Nikolay E. Shirokikh
Kirk Blomquist Jensen
Nehal Thakor- 1The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
- 2School of Biological Sciences, Faculty of Sciences, University of Adelaide, Adelaide, SA, Australia
- 3Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, AB, Canada
Editorial on the Research Topic
RNA machines
The omnipotent RNA machines
RNA has been escaping the limelight for decades while it was used to decipher the genetic code (Gardner et al., 1962; Nirenberg et al., 1965; Nirenberg, 2004), establish the rules of complementary nucleotide pairing (Magasanik et al., 1950), develop sequencing techniques (Jou et al., 1972), showcase foundational biomolecule interactions (Fox et al., 2018; Tauber et al., 2020) and assist in protein production (Spirin et al., 1988). The central dogma of molecular biology, an information flow typical to all living things, has been conceived to be centred around RNA (Boivin and Vendrely, 1947). Yet even now, we often employ a term “encoded in the DNA”, whereas the actual code is written in the RNA and its decoding is also performed by the ancient RNA molecular machinery of the cells. Notably, newer molecule types, classes and functions consistently emerge and re-emerge in the RNA world. The expanding diversity of RNA modifications and the new varieties of “nonocoding” but information-rich RNA remain as a vast and constantly replenisheable reservoir of biologically active molecules (Mercer et al., 2009; Roundtree et al., 2017). RNA now has been intertwined in more and more intricate cellular and viral processes and activities, tying it into the majority–perhaps, all–of the biological pathways.
Refinement of splicing by and for RNA
A fundamentally distinctive feature of the RNA is its versatility. Consequently, we find the involvement of RNA function across all stages of gene expression. In eukaryotic and some prokaryotic cells, RNA-determined splicing is one of the cornerstone processes of gene expression. Splicing is driven by introns which likely originate from ancient retroelements (RNA retroviruses derivatives) but now are tightly controlled in the cells (Xiong and Eickbush, 1990; Flavell, 1995; Boeke and Stoye, 1997; Koonin, 2006; Hoskins and Moore, 2012; Zimmerly and Semper, 2015). Regulation of intron activity during splicing, such as in alternative splicing, creates an extra layer of diversity which is evolutionarily malleable and is thought to be extremely important in cell differentiation of complex organisms such as vertebrates, and in complex organs such as the brain (Santoni et al., 1989; Hoskins and Moore, 2012; Braunschweig et al., 2013; Irimia et al., 2014; Weatheritt et al., 2016; Ha et al., 2021). Interrupted genes themselves and splicing have been discovered relatively early in eukaryotic viruses, and then in the genomes of eukaryotic and some prokaryotic cells (Berget et al., 1977; Chow et al., 1977; Darnell, 1978; Keller and Noon, 1984; Apirion and Miczak, 1993; Belfort et al., 1995; Herbert and Rich, 1999; Benler and Koonin, 2022; Vosseberg et al., 2022). The constituents and structures of the major (type I) eukaryotic splicing machinery are well-established, and include the small nuclear ribonucleoproteins (snRNPs) U1, U2, U4, U5 and U6, and a number of auxiliary protein factors (Wahl et al., 2009; Will and Lührmann, 2011; Zhao and Pyle, 2017; Kastner et al., 2019; van der Feltz and Hoskins, 2019). The action of snRNA-organised spliceosomal complexes on the introns of nuclear transcripts involves first complex E, where U1 binds to the GU sequence at the 5′splice site donor, U2 Auxiliary Factor 1 binds to the AG sequence at the 3′splice site acceptor, U2 Auxiliary Factor 2 binds polypyrimidine tract between the branch point and 3′splice site, and Splicing Factor 1 binds to the branch point. A series of rearrangements then occurs towards Complex A with U2 binding the branch point, Complex B with U4, U5 and U6 joining and releasing U1, and Complex C with U4 release, lariat formation catalysis by U2 and U6 and then exon ligation (Rogers and Wall, 1980; Maniatis, 1991; Stamm et al., 2005; Wahl et al., 2009; Wang et al., 2015; Kastner et al., 2019). Manuel et al. summarise the impact of alternative splicing on the proteome diversity in a comprehensive review also describing splicing contribution to the generation of noncoding and circular RNAs. They address the important challenges in the prevalence of functional alternative splicing, the artefact-prone difficulties it creates in genome annotations, and the linking between observed RNA splice-types and peptide datasets, including advances and limitations of the current technologies.
Splicing picture was not complete until the alternative “minor” (type II) splicing apparatus has been identified (Tarn and Steitz, 1996; Sharp and Burge, 1997). Initially considered as indeed a “minor” variation that rarely occurs with efficiency and operates with a near-complete own set of snRNPs (U11, U12, U4atac, and U6atac, while U5 remains the same), AU-AC or GU-AG acceptor and donor definitions and the branch sequence, U12-type splicing has been found much more prolific (Park et al., 2016; Moyer et al., 2020; Fast, 2021). While not universally encountered, type II spliceosone and its introns are remarkably conserved (human genome harbours about 700 U12-type introns, but it can be much more (Larue et al., 2021)) and were recently highlighted interacting with the type I splicing machinery in diverse ways. In an insightful review, Akinyi and Frilander enlist cooperation between the U2 and U12 types using the example of SNRNP48 and RNPC3 genes (encoding U11 and U12 proteins) where feedback-stabilised U11 and U12 interactions lead to the recognition of 3′splice site 1 and synthesis of a non-productive, nuclear-retained transcript–as opposed to the use of 3′splice site 2 that results in cytoplasmic export and translation. They further showcase examples of direct competition between U2 and U12 types (for HNRNPLL, ZNF207, C1orf112, NCBP2, PRMT1, dZRSR2/Urp, CTNNBL1, CUL4A, SPAG16, Prospero, SRSF10, MAPK8/9, TMEM87a/b, CENATAC and other genes), or cryptic activation of U2 splicing in a deficit of U12 machinery (for SNRPE, RCD8/EDC4, SLC9A8, MAPK12, LKB1 and other genes), and discuss implications in the context of spliceosomal diseases including Peutz-Jager Syndrome, spondyloepiphyseal dysplasia tarda and Cerebral palsy.
Remarkably, splicing has always been linked to RNA polymerase II transcriptional dynamics (Barrass et al., 2015; Naftelberg et al., 2015; Herzel et al., 2017; Milligan et al., 2017; Ragan et al., 2019). In a similarity to the multitude of transcriptional regulators, splicing is modulated by an array of non-constitutive protein factors (Lin and Fu, 2007; Sapra et al., 2009; Änkö et al., 2012; Vuong et al., 2016). Previously, many of such regulators have been implicated in the production of unusual RNA types such as micro and circular RNA (Melamed et al., 2013; Conn et al., 2015; Salzman, 2016; Eger et al., 2018; Pillman et al., 2018; Ratnadiwakara et al., 2018), cases of alternative processing and splicing of micro-exons (Ustianenko et al., 2017; Torres-Méndez et al., 2019; Head et al., 2021), and are known contributors to the physiologically significant development, differentiation and pathogenesis processes (Irimia et al., 2014; Mochizuki et al., 2021). In an original phylogenetic research article, Huang et al. feature the conservation and diversity of SYF2, an important splicing factor that interacts with cyclin D-type binding-protein 1, a cell cycle regulator at the G1/S transition. SYF2 has been characterised as essential or stimulatory in a variety of proliferative situations, including cancer (Guo et al., 2014; Yan et al., 2015; Zhang et al., 2015). Huang et al. demonstrate conservation of the phylogenetic and splicing patterns of SYF2 in animals, while its mRNA abundance patterns were substantially different across the different tissues of mammals. They demonstrate SYF2 is associated with the occurrence of cancer in breast, lung, spleen and reproductive organs, making SYF2 and its RNA interactors valuable therapeutic targets.
RNA regulators conducting without a code
To act, RNA not necessarily needs to be decoded. Micro RNA and various noncoding RNA functions have been prominent in the transition space from transcriptional to post-transcriptional control and translation (Mehler and Mattick, 2007; Mercer et al., 2009; Änkö and Neugebauer, 2010; Schonrock et al., 2012; Salmanidis et al., 2014; Statello et al., 2021). With the advent of various high-throughput sequencing technologies, we began to substantially broaden the horizons of our understanding towards the “rare” RNA transcript type diversity (Kapranov et al., 2007; Ma et al., 2013; Gil and Ulitsky, 2020). Noncoding RNA of various types have emerged as functionally active in determining cell differentiation and development (Fatica and Bozzoni, 2014). Ni et al. dive into the classification of Terminus-Associated Non-coding RNAs (TANRs; as well as mRNA 5′-end associated noncoding RNAs) in an insightful review of these emerging RNA types. They highlight Terminus-Associated Short Non-coding RNAs (TASRs) and their antisense (aTASRs) varieties, Transcription Termination Site Associated RNAs (TTSa-RNAs), Transcription Boundary-Associated RNAs (TBARs), Terminus-Associated Long RNAs (TALRs) and 3′UTR-associated RNAs (uaRNAs), and explore evidence for their biogenesis, including the same and independent promoter models. Ni et al. further enlist organisation and discovery technology of several prominent TANRs and summarise the demonstrated TANR functions, including transcriptional interference, promoter and terminator juxtapositioning, transcription termination assistance, micro RNA sponging and sequence-directed RNA cleavage and modification. They note that functionally-relevant TANRs can originate also from long noncoding RNA genes, with MALAT1 prominently exemplified by its translation-activating MALAT1-associated small cytoplasmic RNA (MascRNA) (Wilusz et al., 2012).
While individual micro RNAs may appear as less multifaceted regulators and interactors compared to the longer non-coding RNAs, a developing view is that micro RNAs function in networks, collectively targeting the entire pathways of the cells (Gao, 2008; Ryan et al., 2010; Bracken et al., 2016; Dragomir et al., 2018). Such networks offer a high degree of versatility, sophistication and accuracy of control. An interesting expansion of this idea is presented in a review of Budrass et al. where they thoroughly describe a new micro RNA regulation network and intersect it with the protein control network of a matching complexity, as found for the chaperones Heat Shock Protein 40s (Hsp40s; often referred to as J-proteins by their encoding DNAJ genes) (Laufen et al., 1999; Han and Christen, 2003). J-proteins are extremely conserved (from bacteria to human) and function as a “tailoring kit” for situationally activating Hsp70 proteins that have far less client discrimination. J-proteins are devise (over 40 in humans) and possess specific client binding, localisation and additional enzymatic activities (Cyr et al., 1994; Jiang et al., 2019). Budrass et al. review micro RNA target site predictions in J-protein mRNAs, demonstrate their conservation across mammals as well as vertebrates, and intriguingly showcase co-targeting of certain J-protein mRNAs (including DNAJ A1, A2, B1, B4, B5, B6b, B9, C13, C21, and C23) by micro RNAs of identical and different families, at one or multiple sites, opening new area of complex combinatorial regulatory opportunities.
Translation of RNA and damage control
Decoding of the messenger(m)RNA into the proteins is the most crucial function performed by the RNA (Topisirovic and Sonenberg, 2011; Hershey et al., 2012; Shirokikh, 2022). Translational control is involved in nutrient, stress condition and damage sensing (Holcik and Sonenberg, 2005; Bramham et al., 2016; Ross et al., 2018; 2019; Janapala et al., 2019; Xie et al., 2019). Translation employs the most complete repertoire of RNA activities, including direct basepairing interactions, complex structure formation, functionally modified nucleotides, energised intermediates such as the aminoacyl-tRNA, precise macromolecular interactions as happens in the ribosomal subunit binding and elongation cycle dynamics, and ribozyme catalysis in the ribosomal peptidyl transferase centre. Translation initiation is the most responsive protein biosynthesis regulator in eukaryotes (Kozak, 1992; Pisarev et al., 2005; Sonenberg and Hinnebusch, 2009; Archer et al., 2016; Shirokikh and Preiss, 2018), and within it the accuracy of start codon recognition is especially important, whereby a small mistake can lead to misfolded proteins and adverse cell effects including malignancy (Fekete et al., 2005; Lomakin et al., 2006; Cheung et al., 2007; Asano, 2014; Thakur et al., 2020; Gleason et al., 2022). Accurate start codon recognition involves protein initiator tRNA “carriers”—of which a GTPase eukaryotic translation initiation factor 5B (eIF5B) is the most conserved, having its bacterial and archaeal counterparts (Ross et al., 2018; Shirokikh and Preiss, 2018). In an immersive mini-review, Chukka et al. discuss eIF5B at the crossroads the ribosomal, transfer and messenger RNA interactions. They highlight canonical and most conserved eIF5B functions in initiator tRNA stabilisation on the ribosomal small subunit and subunit joining. Chukka et al. also provide an outlook into the less obvious eIF5B activities in checkpointing eukaryotic small subunit maturation, conveying initiation with the alternative initiator tRNA carrier eIF2A active in certain stresses and interacting with viral (e.g., hepatitis C virus and classical swine fever virus) and cellular (e.g., X-linked inhibitor of apoptosis) internal ribosome entry sites (IRESes). eIF5B action in upstream Open Reading Frame (uORF)-regulated genes is reviewed and its overall cell survival-promoting and thus, malignancy-maintaining role is brought into the focus as an attractive drug target.
Another interesting activity of RNA tightly linked to translation is that of a cellular protection and damage sensing. Oxygenation and oxidative environments present a substantial challenge to the nucleic acids-based life, and especially so to the RNA which can become oxidised in a diverse ways. It has been known that oxidised RNA induces translational errors and may be neurodegenerative or carcinogenic (Tanaka et al., 2007; Fimognari, 2015; Guo et al., 2020). Seixas et al. thoroughly present types of oxidative RNA damage in a mini review covering the most ubiquitous oxidating agents, RNA injuries including 8-oxo-7,8-dihydroguanosine, 8-oxo-7,8-dihydroadenosine, 5-hydroxycytosine and 5-hydroxyuridine, and their effects on mRNA, tRNA, ribosomal and micro RNA function. Seixas et al. emphasise the known passive (scavenging) and active (repair) RNA injury protection systems in prokaryotes noting open questions in comprehensive identification of these components across all life.
Multifunctional RNA in viruses and synthetic biology
RNA is often multifunctional in viruses where there can be certain restrictions on genome size, and in synthetic biology designs where vector and delivery limitations apply to the RNA length, together with the considerations of economy and cost (Afonin et al., 2014; Rossetto and Pari, 2014; Dao et al., 2015; Richert-Pöggeler et al., 2021). From its discovery, Human Immunodeficiency Virus 1 (HIV-1) has been intriguing the researchers with the multitude of functions of its highly-structured RNA modules, containing proteins in all three open reading frames and often with an overlap (splicing-, scanning-, frameshifting- and shunting-controlled), which can be synthesised from the 5′cap or IRES (Ohlmann et al., 2014; Guerrero et al., 2015; Reitz and Gallo, 2015; De Breyne and Ohlmann, 2019). In the DNA-integrated form the HIV-1 provirus can produce partially-spliced and fully-spliced transcripts, among the latter the tat mRNA, encoding the essential Tat transcriptional regulator of the virus. All viral transcripts share the initial 289 nt and thus the 59 nt of the highly structured trans-activation response (TAR) RNA element. TAR controls host translation via activation and suppression of Protein Kinase RNA-activated (PKR), and further activates viral transcription upon Tat binding (Guerrero et al., 2015). Inspired by their recent discovery that tat can have an IRES element active in latent infection (Khoury et al., 2020), Khoury et al. in an original research article embarked on a tour de force to explore cellular proteins possibly interacting with tat and modulating it. Discovering 243 significantly interacting proteins by tat-3×MS2-stem-loop-directed pull-down and mass spectrometry in latent and productive T-cells, they used knockdown of several top hits to identify Signal Recognition Particle 14 (SRP14) and High-mobility group box 3 (HMGB3) proteins affecting HIV infection the most. Using RNA modification protection, Khoury et al. located the SRP14 and HMGB3 binding sites nearby the tat start codon. Most intriguingly, SRP14 and HMGB3 negatively regulated latent and productive infection, while stimulating and repressing Tat synthesis, respectively. Khoury et al. propose SRP14 and HMGB3 alter the efficiency of the tat IRES, opening new depths in the lentiviral host interactions and additional pathways to manipulate HIV reactivation.
Interestingly, HIV-1 RNA may contain other RNA regulators, riboswitches (Ooms et al., 2004; Boeras et al., 2017). Riboswitches are compact structural modules of RNA conditionally obstructing (or promoting) a certain process (Garst et al., 2011; Breaker, 2012). Riboswitches can be sensitive to an interaction with another macromolecule or a small compound, or physical conditions such as temperature, pH, salinity, etc., (Mironov et al., 2002; Nahvi et al., 2002; Serganov and Nudler, 2013). Riboswitches can be placed ahead of an “amplifying” stage of a synthetic construct expression, such as transcription or translation, and thus are among the most interesting synthetic biology tools (Breaker, 2018; Kavita and Breaker, 2022). In a brief research report, Korniakova et al. present a new fluoride-sensitive vector design incorporating a fluoride riboswitch (Ren et al., 2012) in the reporter 5′UTR, downstream of the testable promoter region. The plasmid allows to decouple cloning of powerful and potentially cell-damaging promoters from their functional testing, while maintaining same arrangement of the vector for the ease of cloning and comparisons.
Perspectives for RNA as a molecular machine of design
It may not be an overstatement to name the RNA an ultimate molecular machine of life. RNA often performs in relatively straightforward ways built on direct molecular recognition through tertiary structure and basepairing, as happens during micro RNA target binding, and in distinct enzymatic reactions, as occurs during the intron lariat formation and excision. In the other cases, RNA performs as the structural and enzymatic core of conveying molecular machines such as the ribosome, where it uses chemical energy to process, transform and realise biological information. It is quite remarkable that the RNA can “work” with all types of biological macromolecules, be an enzyme and a substrate, carry and decode the genetic information, signal, receive and operate with chemical potentials, making it a “complete”, self-sufficient molecule. This self-sufficiency contains a value for novel synthetic biology designs, that is, being recognised in RNA vaccines and gene replacement therapeutics of more sophisticated construction, such as self-amplifying RNA (Rodríguez-Gascón et al., 2014; Brito et al., 2015; Pardi et al., 2018; Dolgin, 2021). It also contains a substantial combinatorial challenge of finding an optimal function in a sea of interactions and activities. We can hope to keep learning from extant (and extinct) life to identify new elements of RNA control, and employ approaches based on artificial intelligence to devise new RNA modules and their applications (Lv et al., 2021; Mohanty and Mohanty, 2021). Thankfully and as exemplified in this Research Topic, we cannot stop to continuously discover new, sometimes unexpected, nuances of the RNA-based processes.
Author contributions
NS: Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing–original draft, Writing–review and editing. KJ: Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing–original draft, Writing–review and editing. NT: Conceptualization, Funding acquisition, Investigation, Project administration, Resources, Supervision, Writing–original draft, Writing–review and editing.
Funding
This work was supported by the National Health and Medical Research Council (NHMRC) Investigator grant (GNT1175388) and The Bootes Foundation grant (to NS); New Frontiers in Research Fund Exploration grant (NFRFE-2019-01047), the Natural Sciences and Engineering Research Council of Canada-Discovery Grant Program (RGPIN-2017-05463) (to NT).
Acknowledgments
The authors acknowledge the support of their group members in preparing the manuscript.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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References
Afonin, K. A., Viard, M., Koyfman, A. Y., Martins, A. N., Kasprzak, W. K., Panigaj, M., et al. (2014). Multifunctional RNA nanoparticles. Nano Lett. 14, 5662–5671. doi:10.1021/nl502385k
Änkö, M.-L., Müller-McNicoll, M., Brandl, H., Curk, T., Gorup, C., Henry, I., et al. (2012). The RNA-binding landscapes of two SR proteins reveal unique functions and binding to diverse RNA classes. Genome Biol. 13, R17. doi:10.1186/gb-2012-13-3-r17
Änkö, M.-L., and Neugebauer, K. M. (2010). Long noncoding RNAs add another layer to pre-mRNA splicing regulation. Mol. Cell 39, 833–834. doi:10.1016/j.molcel.2010.09.003
Apirion, D., and Miczak, A. (1993). RNA processing in prokaryotic cells. BioEssays 15, 113–120. doi:10.1002/bies.950150207
Archer, S. K., Shirokikh, N. E., Beilharz, T. H., and Preiss, T. (2016). Dynamics of ribosome scanning and recycling revealed by translation complex profiling. Nature 535, 570–574. doi:10.1038/nature18647
Asano, K. (2014). Why is start codon selection so precise in eukaryotes? Translation 2, e28387. doi:10.4161/trla.28387
Barrass, J. D., Reid, J. E. A., Huang, Y., Hector, R. D., Sanguinetti, G., Beggs, J. D., et al. (2015). Transcriptome-wide RNA processing kinetics revealed using extremely short 4tU labeling. Genome Biol. 16, 282. doi:10.1186/s13059-015-0848-1
Belfort, M., Reaban, M. E., Coetzee, T., and Dalgaard, J. Z. (1995). Prokaryotic introns and inteins: A panoply of form and function. J. Bacteriol. 177, 3897–3903. doi:10.1128/jb.177.14.3897-3903.1995
Benler, S., and Koonin, E. V. (2022). Recruitment of mobile genetic elements for diverse cellular functions in prokaryotes. Front. Mol. Biosci. 9, 821197. doi:10.3389/fmolb.2022.821197
Berget, S. M., Moore, C., and Sharp, P. A. (1977). Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Proc. Natl. Acad. Sci. 74, 3171–3175. doi:10.1073/pnas.74.8.3171
Boeke, J., and Stoye, J. (1997). Retrotransposons, endogenous retroviruses, and the evolution of retroelement. Available at: https://www.ncbi.nlm.nih.gov/books/NBK19468 (Accessed January 7, 2023).
Boeras, I., Seufzer, B., Brady, S., Rendahl, A., Heng, X., and Boris-Lawrie, K. (2017). The basal translation rate of authentic HIV-1 RNA is regulated by 5’UTR nt-pairings at junction of R and U5. Sci. Rep. 7, 6902. doi:10.1038/s41598-017-06883-9
Boivin, A., and Vendrely, R. (1947). On the possible role of the two nuclear acids in the living cell. Experientia 3, 32–34. doi:10.1007/BF02155119
Bracken, C. P., Scott, H. S., and Goodall, G. J. (2016). A network-biology perspective of microRNA function and dysfunction in cancer. Nat. Rev. Genet. 17, 719–732. doi:10.1038/nrg.2016.134
Bramham, C. R., Jensen, K. B., and Proud, C. G. (2016). Tuning specific translation in cancer metastasis and synaptic memory: control at the MNK–eIF4E Axis. Trends Biochem. Sci. 41, 847–858. doi:10.1016/j.tibs.2016.07.008
Braunschweig, U., Gueroussov, S., Plocik, A. M., Graveley, B. R., and Blencowe, B. J. (2013). Dynamic integration of splicing within gene regulatory pathways. Cell 152, 1252–1269. doi:10.1016/j.cell.2013.02.034
Breaker, R. R. (2012). Riboswitches and the RNA world. Cold Spring Harb. Perspect. Biol. 4, a003566. doi:10.1101/cshperspect.a003566
Breaker, R. R. (2018). Riboswitches and translation control. Cold Spring Harb. Perspect. Biol. 10, a032797. doi:10.1101/cshperspect.a032797
Brito, L. A., Kommareddy, S., Maione, D., Uematsu, Y., Giovani, C., Berlanda Scorza, F., et al. (2015). “Chapter seven - self-amplifying mRNA vaccines,” in Advances in genetics nonviral vectors for gene therapy. Editors L. Huang, D. Liu, and E. Wagner (Cambridge, MA: Academic Press), 179–233. doi:10.1016/bs.adgen.2014.10.005
Cheung, Y.-N., Maag, D., Mitchell, S. F., Fekete, C. A., Algire, M. A., Takacs, J. E., et al. (2007). Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivo. Genes Dev. 21, 1217–1230. doi:10.1101/gad.1528307
Chow, L. T., Gelinas, R. E., Broker, T. R., and Roberts, R. J. (1977). An amazing sequence arrangement at the 5’ ends of adenovirus 2 messenger RNA. Cell 12, 1–8. doi:10.1016/0092-8674(77)90180-5
Conn, S. J., Pillman, K. A., Toubia, J., Conn, V. M., Salmanidis, M., Phillips, C. A., et al. (2015). The RNA binding protein quaking regulates formation of circRNAs. Cell 160, 1125–1134. doi:10.1016/j.cell.2015.02.014
Cyr, D. M., Langer, T., and Douglas, M. G. (1994). DnaJ-like proteins: molecular chaperones and specific regulators of Hsp70. Trends Biochem. Sci. 19, 176–181. doi:10.1016/0968-0004(94)90281-X
Dao, B. N., Viard, M., Martins, A. N., Kasprzak, W. K., Shapiro, B. A., and Afonin, K. A. (2015). Triggering RNAi with multifunctional RNA nanoparticles and their delivery. DNA RNA Nanotechnol. 2, 1–12. doi:10.1515/rnan-2015-0001
Darnell, J. E. (1978). Implications of RNA⋅RNA splicing in evolution of eukaryotic cells. Science 202, 1257–1260. doi:10.1126/science.364651
De Breyne, S., and Ohlmann, T. (2019). Focus on translation initiation of the HIV-1 mRNAs. Int. J. Mol. Sci. 20, 101. doi:10.3390/ijms20010101
Dolgin, E. (2021). The tangled history of mRNA vaccines. Nature 597, 318–324. doi:10.1038/d41586-021-02483-w
Dragomir, M., Mafra, A. C. P., Dias, S. M. G., Vasilescu, C., and Calin, G. A. (2018). Using microRNA networks to understand cancer. Int. J. Mol. Sci. 19, 1871. doi:10.3390/ijms19071871
Eger, N., Schoppe, L., Schuster, S., Laufs, U., and Boeckel, J.-N. (2018). “Circular RNA splicing,” in Circular RNAs: Biogenesis and functions advances in experimental medicine and biology. Editor J. Xiao (Singapore: Springer), 41–52. doi:10.1007/978-981-13-1426-1_4
Fast, N. M. (2021). Intron splicing: U12 spliceosomal introns not so ‘minor’ after all. Curr. Biol. 31, R912–R914. doi:10.1016/j.cub.2021.06.008
Fatica, A., and Bozzoni, I. (2014). Long non-coding RNAs: new players in cell differentiation and development. Nat. Rev. Genet. 15, 7–21. doi:10.1038/nrg3606
Fekete, C. A., Applefield, D. J., Blakely, S. A., Shirokikh, N., Pestova, T., Lorsch, J. R., et al. (2005). The eIF1A C-terminal domain promotes initiation complex assembly, scanning and AUG selection in vivo. EMBO J. 24, 3588–3601. doi:10.1038/sj.emboj.7600821
Fimognari, C. (2015). Role of oxidative RNA damage in chronic-degenerative diseases. Oxidative Med. Cell. Longev. 2015, e358713. doi:10.1155/2015/358713
Flavell, A. J. (1995). Retroelements, reverse transcriptase and evolution. Comp. Biochem. Physiology Part B Biochem. Mol. Biol. 110, 3–15. doi:10.1016/0305-0491(94)00122-B
Fox, A. H., Nakagawa, S., Hirose, T., and Bond, C. S. (2018). Paraspeckles: where long noncoding RNA meets phase separation. Trends Biochem. Sci. 43, 124–135. doi:10.1016/j.tibs.2017.12.001
Gao, F.-B. (2008). Posttranscriptional control of neuronal development by microRNA networks. Trends Neurosci. 31, 20–26. doi:10.1016/j.tins.2007.10.004
Gardner, R. S., Wahba, A. J., Basilio, C., Miller, R. S., Lengyel, P., and Speyer, J. F. (1962). Synthetic polynucleotides and the amino acid code, vii. Proc. Natl. Acad. Sci. 48, 2087–2094. doi:10.1073/pnas.48.12.2087
Garst, A. D., Edwards, A. L., and Batey, R. T. (2011). Riboswitches: structures and mechanisms. Cold Spring Harb. Perspect. Biol. 3, a003533. doi:10.1101/cshperspect.a003533
Gil, N., and Ulitsky, I. (2020). Regulation of gene expression by cis-acting long non-coding RNAs. Nat. Rev. Genet. 21, 102–117. doi:10.1038/s41576-019-0184-5
Gleason, A. C., Ghadge, G., Sonobe, Y., and Roos, R. P. (2022). Kozak similarity score algorithm identifies alternative translation initiation codons implicated in cancers. Int. J. Mol. Sci. 23, 10564. doi:10.3390/ijms231810564
Guerrero, S., Batisse, J., Libre, C., Bernacchi, S., Marquet, R., and Paillart, J.-C. (2015). HIV-1 replication and the cellular eukaryotic translation apparatus. Viruses 7, 199–218. doi:10.3390/v7010199
Guo, C., Chen, Q., Chen, J., Yu, J., Hu, Y., Zhang, S., et al. (2020). 8-Hydroxyguanosine as a possible RNA oxidative modification marker in urine from colorectal cancer patients: evaluation by ultra performance liquid chromatography-tandem mass spectrometry. J. Chromatogr. B 1136, 121931. doi:10.1016/j.jchromb.2019.121931
Guo, J., Yang, L., Huang, J., Liu, X., Qiu, X., Tao, T., et al. (2014). Knocking down the expression of SYF2 inhibits the proliferation of glioma cells. Med. Oncol. 31, 101. doi:10.1007/s12032-014-0101-x
Ha, K. C. H., Sterne-Weiler, T., Morris, Q., Weatheritt, R. J., and Blencowe, B. J. (2021). Differential contribution of transcriptomic regulatory layers in the definition of neuronal identity. Nat. Commun. 12, 335. doi:10.1038/s41467-020-20483-8
Han, W., and Christen, P. (2003). Mechanism of the targeting action of DnaJ in the DnaK molecular chaperone system. J. Biol. Chem. 278, 19038–19043. doi:10.1074/jbc.M300756200
Head, S. A., Hernandez-Alias, X., Yang, J.-S., Ciampi, L., Beltran-Sastre, V., Torres-Méndez, A., et al. (2021). Silencing of SRRM4 suppresses microexon inclusion and promotes tumor growth across cancers. PLOS Biol. 19, e3001138. doi:10.1371/journal.pbio.3001138
Herbert, A., and Rich, A. (1999). RNA processing and the evolution of eukaryotes. Nat. Genet. 21, 265–269. doi:10.1038/6780
Hershey, J. W. B., Sonenberg, N., and Mathews, M. B. (2012). Principles of translational control: an overview. Cold Spring Harb. Perspect. Biol. 4, a011528. doi:10.1101/cshperspect.a011528
Herzel, L., Ottoz, D. S. M., Alpert, T., and Neugebauer, K. M. (2017). Splicing and transcription touch base: co-transcriptional spliceosome assembly and function. Nat. Rev. Mol. Cell Biol. 18, 637–650. doi:10.1038/nrm.2017.63
Holcik, M., and Sonenberg, N. (2005). Translational control in stress and apoptosis. Nat. Rev. Mol. Cell Biol. 6, 318–327. doi:10.1038/nrm1618
Hoskins, A. A., and Moore, M. J. (2012). The spliceosome: A flexible, reversible macromolecular machine. Trends Biochem. Sci. 37, 179–188. doi:10.1016/j.tibs.2012.02.009
Irimia, M., Weatheritt, R. J., Ellis, J. D., Parikshak, N. N., Gonatopoulos-Pournatzis, T., Babor, M., et al. (2014). A highly conserved Program of neuronal microexons is misregulated in autistic brains. Cell 159, 1511–1523. doi:10.1016/j.cell.2014.11.035
Janapala, Y., Preiss, T., and Shirokikh, N. E. (2019). Control of translation at the initiation phase during glucose starvation in yeast. Int. J. Mol. Sci. 20, 4043. doi:10.3390/ijms20164043
Jiang, Y., Rossi, P., and Kalodimos, C. G. (2019). Structural basis for client recognition and activity of Hsp40 chaperones. Science 365, 1313–1319. doi:10.1126/science.aax1280
Jou, W. M., Haegeman, G., Ysebaert, M., and Fiers, W. (1972). Nucleotide sequence of the gene coding for the bacteriophage MS2 coat protein. Nature 237, 82–88. doi:10.1038/237082a0
Kapranov, P., Cheng, J., Dike, S., Nix, D. A., Duttagupta, R., Willingham, A. T., et al. (2007). RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316, 1484–1488. doi:10.1126/science.1138341
Kastner, B., Will, C. L., Stark, H., and Lührmann, R. (2019). Structural insights into nuclear pre-mRNA splicing in higher eukaryotes. Cold Spring Harb. Perspect. Biol. 11, a032417. doi:10.1101/cshperspect.a032417
Kavita, K., and Breaker, R. R. (2022). Discovering riboswitches: the past and the future. Trends Biochem. Sci. 48, 119–141. doi:10.1016/j.tibs.2022.08.009
Keller, E. B., and Noon, W. A. (1984). Intron splicing: A conserved internal signal in introns of animal pre-mRNAs. Proc. Natl. Acad. Sci. 81, 7417–7420. doi:10.1073/pnas.81.23.7417
Khoury, G., Mackenzie, C., Ayadi, L., Lewin, S. R., Branlant, C., and Purcell, D. F. J. (2020). Tat IRES modulator of tat mRNA (TIM-TAM): A conserved RNA structure that controls tat expression and acts as a switch for HIV productive and latent infection. Nucleic Acids Res. 48, 2643–2660. doi:10.1093/nar/gkz1181
Koonin, E. V. (2006). The origin of introns and their role in eukaryogenesis: A compromise solution to the introns-early versus introns-late debate? Biol. Direct 1, 22. doi:10.1186/1745-6150-1-22
Kozak, M. (1992). Regulation of translation in eukaryotic systems. Annu. Rev. Cell Biol. 8, 197–225. doi:10.1146/annurev.cb.08.110192.001213
Larue, G. E., Eliáš, M., and Roy, S. W. (2021). Expansion and transformation of the minor spliceosomal system in the slime mold Physarum polycephalum. Curr. Biol. 31, 3125–3131.e4. doi:10.1016/j.cub.2021.04.050
Laufen, T., Mayer, M. P., Beisel, C., Klostermeier, D., Mogk, A., Reinstein, J., et al. (1999). Mechanism of regulation of Hsp70 chaperones by DnaJ cochaperones. Proc. Natl. Acad. Sci. 96, 5452–5457. doi:10.1073/pnas.96.10.5452
Lin, S., and Fu, X.-D. (2007). SR proteins and related factors in alternative splicing. Adv. Exp. Med. Biol. 623, 107–122. doi:10.1007/978-0-387-77374-2_7
Lomakin, I. B., Shirokikh, N. E., Yusupov, M. M., Hellen, C. U., and Pestova, T. V. (2006). The fidelity of translation initiation: reciprocal activities of eIF1, IF3 and YciH. EMBO J. 25, 196–210. doi:10.1038/sj.emboj.7600904
Lv, H., Shi, L., Berkenpas, J. W., Dao, F.-Y., Zulfiqar, H., Ding, H., et al. (2021). Application of artificial intelligence and machine learning for COVID-19 drug discovery and vaccine design. Briefings Bioinforma. 22, bbab320. doi:10.1093/bib/bbab320
Ma, L., Bajic, V. B., and Zhang, Z. (2013). On the classification of long non-coding RNAs. RNA Biol. 10, 925–933. doi:10.4161/rna.24604
Magasanik, B., Vischer, E., Doniger, R., Elson, D., and Chargaff, E. (1950). The separation and estimation of ribonucleotides in minute quantities. J. Biol. Chem. 186, 37–50. doi:10.1016/s0021-9258(18)56284-0
Maniatis, T. (1991). Mechanisms of alternative pre-mRNA splicing. Science 251, 33–34. doi:10.1126/science.1824726
Mehler, M. F., and Mattick, J. S. (2007). Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease. Physiol. Rev. 87, 799–823. doi:10.1152/physrev.00036.2006
Melamed, Z., Levy, A., Ashwal-Fluss, R., Lev-Maor, G., Mekahel, K., Atias, N., et al. (2013). Alternative splicing regulates biogenesis of miRNAs located across exon-intron junctions. Mol. Cell 50, 869–881. doi:10.1016/j.molcel.2013.05.007
Mercer, T. R., Dinger, M. E., and Mattick, J. S. (2009). Long non-coding RNAs: insights into functions. Nat. Rev. Genet. 10, 155–159. doi:10.1038/nrg2521
Milligan, L., Sayou, C., Tuck, A., Auchynnikava, T., Reid, J. E., Alexander, R., et al. (2017). RNA polymerase II stalling at pre-mRNA splice sites is enforced by ubiquitination of the catalytic subunit. eLife 6, e27082. doi:10.7554/eLife.27082
Mironov, A. S., Gusarov, I., Rafikov, R., Lopez, L. E., Shatalin, K., Kreneva, R. A., et al. (2002). Sensing small molecules by nascent RNA: A mechanism to control transcription in bacteria. Cell 111, 747–756. doi:10.1016/S0092-8674(02)01134-0
Mochizuki, Y., Funayama, R., Shirota, M., Kikukawa, Y., Ohira, M., Karasawa, H., et al. (2021). Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer. Int. J. Cancer 149, 1787–1800. doi:10.1002/ijc.33758
Mohanty, E., and Mohanty, A. (2021). Role of artificial intelligence in peptide vaccine design against RNA viruses. Inf. Med. Unlocked 26, 100768. doi:10.1016/j.imu.2021.100768
Moyer, D. C., Larue, G. E., Hershberger, C. E., Roy, S. W., and Padgett, R. A. (2020). Comprehensive database and evolutionary dynamics of U12-type introns. Nucleic Acids Res. 48, 7066–7078. doi:10.1093/nar/gkaa464
Naftelberg, S., Schor, I. E., Ast, G., and Kornblihtt, A. R. (2015). Regulation of alternative splicing through coupling with transcription and chromatin structure. Annu. Rev. Biochem. 84, 165–198. doi:10.1146/annurev-biochem-060614-034242
Nahvi, A., Sudarsan, N., Ebert, M. S., Zou, X., Brown, K. L., and Breaker, R. R. (2002). Genetic control by a metabolite binding mRNA. Chem. Biol. 9, 1043–1049. doi:10.1016/S1074-5521(02)00224-7
Nirenberg, M. (2004). Historical review: deciphering the genetic code – a personal account. Trends Biochem. Sci. 29, 46–54. doi:10.1016/j.tibs.2003.11.009
Nirenberg, M., Leder, P., Bernfield, M., Brimacombe, R., Trupin, J., Rottman, F., et al. (1965). RNA codewords and protein synthesis, VII. On the general nature of the RNA code. Proc. Natl. Acad. Sci. U. S. A. 53, 1161–1168. doi:10.1073/pnas.53.5.1161
Ohlmann, T., Mengardi, C., and López-Lastra, M. (2014). Translation initiation of the HIV-1 mRNA. Transl. (Austin) 2, e960242. doi:10.4161/2169074X.2014.960242
Ooms, M., Huthoff, H., Russell, R., Liang, C., and Berkhout, B. (2004). A riboswitch regulates RNA dimerization and packaging in human immunodeficiency virus type 1 virions. J. Virol. 78, 10814–10819. doi:10.1128/JVI.78.19.10814-10819.2004
Pardi, N., Hogan, M. J., Porter, F. W., and Weissman, D. (2018). mRNA vaccines — A new era in vaccinology. Nat. Rev. Drug Discov. 17, 261–279. doi:10.1038/nrd.2017.243
Park, S. J., Jung, H. J., Nguyen Dinh, S., and Kang, H. (2016). Structural features important for the U12 snRNA binding and minor spliceosome assembly of Arabidopsis U11/U12-small nuclear ribonucleoproteins. RNA Biol. 13, 670–679. doi:10.1080/15476286.2016.1191736
Pillman, K. A., Phillips, C. A., Roslan, S., Toubia, J., Dredge, B. K., Bert, A. G., et al. (2018). miR-200/375 control epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking. EMBO J. 37, e99016. doi:10.15252/embj.201899016
Pisarev, A. V., Shirokikh, N. E., and Hellen, C. U. T. (2005). Translation initiation by factor-independent binding of eukaryotic ribosomes to internal ribosomal entry sites. Comptes Rendus Biol. 328, 589–605. doi:10.1016/j.crvi.2005.02.004
Ragan, C., Goodall, G. J., Shirokikh, N. E., and Preiss, T. (2019). Insights into the biogenesis and potential functions of exonic circular RNA. Sci. Rep. 9, 2048. doi:10.1038/s41598-018-37037-0
Ratnadiwakara, M., Mohenska, M., and Änkö, M.-L. (2018). Splicing factors as regulators of miRNA biogenesis – links to human disease. Seminars Cell & Dev. Biol. 79, 113–122. doi:10.1016/j.semcdb.2017.10.008
Reitz, M. S., and Gallo, R. C. (2015). “171 - human immunodeficiency viruses,” in Mandell, douglas, and bennett’s principles and practice of infectious diseases. Editors J. E. Bennett, R. Dolin, and M. J. Blaser (Philadelphia: W.B. Saunders), 2054–2065. doi:10.1016/B978-1-4557-4801-3.00171-5
Ren, A., Rajashankar, K. R., and Patel, D. J. (2012). Fluoride ion encapsulation by Mg2+ ions and phosphates in a fluoride riboswitch. Nature 486, 85–89. doi:10.1038/nature11152
Richert-Pöggeler, K. R., Vijverberg, K., Alisawi, O., Chofong, G. N., Heslop-Harrison, J. S., Pat), , and Schwarzacher, T. (2021). Participation of multifunctional RNA in replication, recombination and regulation of endogenous plant pararetroviruses (EPRVs). Front. Plant Sci. 12, 689307. doi:10.3389/fpls.2021.689307
Rodríguez-Gascón, A., del Pozo-Rodríguez, A., and Solinís, M. Á. (2014). Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles. Int. J. Nanomedicine 9, 1833–1843. doi:10.2147/IJN.S39810
Rogers, J., and Wall, R. (1980). A mechanism for RNA splicing. Proc. Natl. Acad. Sci. 77, 1877–1879. doi:10.1073/pnas.77.4.1877
Ross, J. A., Bressler, K. R., and Thakor, N. (2018). Eukaryotic initiation factor 5B (eIF5B) cooperates with eIF1A and eIF5 to facilitate uORF2-mediated repression of ATF4 translation. Int. J. Mol. Sci. 19, 4032. doi:10.3390/ijms19124032
Ross, J. A., Dungen, K. V., Bressler, K. R., Fredriksen, M., Khandige Sharma, D., Balasingam, N., et al. (2019). Eukaryotic initiation factor 5B (eIF5B) provides a critical cell survival switch to glioblastoma cells via regulation of apoptosis. Cell Death Dis. 10, 57–15. doi:10.1038/s41419-018-1283-5
Rossetto, C. C., and Pari, G. S. (2014). PAN’s labyrinth: molecular biology of kaposi’s sarcoma-associated herpesvirus (KSHV) PAN RNA, a multifunctional long noncoding RNA. Viruses 6, 4212–4226. doi:10.3390/v6114212
Roundtree, I. A., Evans, M. E., Pan, T., and He, C. (2017). Dynamic RNA modifications in gene expression regulation. Cell 169, 1187–1200. doi:10.1016/j.cell.2017.05.045
Ryan, B. M., Robles, A. I., and Harris, C. C. (2010). Genetic variation in microRNA networks: the implications for cancer research. Nat. Rev. Cancer 10, 389–402. doi:10.1038/nrc2867
Salmanidis, M., Pillman, K., Goodall, G., and Bracken, C. (2014). Direct transcriptional regulation by nuclear microRNAs. Int. J. Biochem. Cell Biol. 54, 304–311. doi:10.1016/j.biocel.2014.03.010
Salzman, J. (2016). Circular RNA expression: its potential regulation and function. Trends Genet. 32, 309–316. doi:10.1016/j.tig.2016.03.002
Santoni, M. J., Barthels, D., Vopper, G., Boned, A., Goridis, C., and Wille, W. (1989). Differential exon usage involving an unusual splicing mechanism generates at least eight types of NCAM cDNA in mouse brain. EMBO J. 8, 385–392. doi:10.1002/j.1460-2075.1989.tb03389.x
Sapra, A. K., Änkö, M.-L., Grishina, I., Lorenz, M., Pabis, M., Poser, I., et al. (2009). SR protein family members display diverse activities in the formation of nascent and mature mRNPs in vivo. Mol. Cell 34, 179–190. doi:10.1016/j.molcel.2009.02.031
Schonrock, N., Harvey, R. P., and Mattick, J. S. (2012). Long noncoding RNAs in cardiac development and pathophysiology. Circulation Res. 111, 1349–1362. doi:10.1161/CIRCRESAHA.112.268953
Serganov, A., and Nudler, E. (2013). A decade of riboswitches. Cell 152, 17–24. doi:10.1016/j.cell.2012.12.024
Sharp, P. A., and Burge, C. B. (1997). Classification of introns: U2-Type or U12-type. Cell 91, 875–879. doi:10.1016/S0092-8674(00)80479-1
Shirokikh, N. E., and Preiss, T. (2018). Translation initiation by cap-dependent ribosome recruitment: recent insights and open questions. WIREs RNA 9, e1473. doi:10.1002/wrna.1473
Shirokikh, N. E. (2022). Translation complex stabilization on messenger RNA and footprint profiling to study the RNA responses and dynamics of protein biosynthesis in the cells. Crit. Rev. Biochem. Mol. Biol. 57, 261–304. doi:10.1080/10409238.2021.2006599
Sonenberg, N., and Hinnebusch, A. G. (2009). Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136, 731–745. doi:10.1016/j.cell.2009.01.042
Spirin, A. S., Baranov, V. I., Ryabova, L. A., Ovodov, S., and Alakhov, Y. B. (1988). A continuous cell-free translation system capable of producing polypeptides in high yield. Science 242, 1162–1164. doi:10.1126/science.3055301
Stamm, S., Ben-Ari, S., Rafalska, I., Tang, Y., Zhang, Z., Toiber, D., et al. (2005). Function of alternative splicing. Gene 344, 1–20. doi:10.1016/j.gene.2004.10.022
Statello, L., Guo, C.-J., Chen, L.-L., and Huarte, M. (2021). Gene regulation by long non-coding RNAs and its biological functions. Nat. Rev. Mol. Cell Biol. 22, 96–118. doi:10.1038/s41580-020-00315-9
Tanaka, M., Chock, P. B., and Stadtman, E. R. (2007). Oxidized messenger RNA induces translation errors. Proc. Natl. Acad. Sci. 104, 66–71. doi:10.1073/pnas.0609737104
Tarn, W.-Y., and Steitz, J. A. (1996). A novel spliceosome containing U11, U12, and U5 snRNPs excises a minor class (AT–AC) intron in vitro. Cell 84, 801–811. doi:10.1016/S0092-8674(00)81057-0
Tauber, D., Tauber, G., Khong, A., Van Treeck, B., Pelletier, J., and Parker, R. (2020). Modulation of RNA condensation by the DEAD-box protein eIF4A. Cell 180, 411–426. doi:10.1016/j.cell.2019.12.031
Thakur, A., Gaikwad, S., Vijjamarri, A. K., and Hinnebusch, A. G. (2020). eIF2α interactions with mRNA control accurate start codon selection by the translation preinitiation complex. Nucleic Acids Res. 48, 10280–10296. doi:10.1093/nar/gkaa761
Topisirovic, I., and Sonenberg, N. (2011). Translational control by the eukaryotic ribosome. Cell 145, 333–334. doi:10.1016/j.cell.2011.04.006
Torres-Méndez, A., Bonnal, S., Marquez, Y., Roth, J., Iglesias, M., Permanyer, J., et al. (2019). A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons. Nat. Ecol. Evol. 3, 691–701. doi:10.1038/s41559-019-0813-6
Ustianenko, D., Weyn-Vanhentenryck, S. M., and Zhang, C. (2017). Microexons: discovery, regulation, and function. WIREs RNA 8, e1418. doi:10.1002/wrna.1418
van der Feltz, C., and Hoskins, A. A. (2019). Structural and functional modularity of the U2 snRNP in pre-mRNA splicing. Crit. Rev. Biochem. Mol. Biol. 54, 443–465. doi:10.1080/10409238.2019.1691497
Vosseberg, J., Schinkel, M., Gremmen, S., and Snel, B. (2022). The spread of the first introns in proto-eukaryotic paralogs. Commun. Biol. 5, 476–479. doi:10.1038/s42003-022-03426-5
Vuong, C. K., Black, D. L., and Zheng, S. (2016). The neurogenetics of alternative splicing. Nat. Rev. Neurosci. 17, 265–281. doi:10.1038/nrn.2016.27
Wahl, M. C., Will, C. L., and Lührmann, R. (2009). The spliceosome: design principles of a dynamic RNP machine. Cell 136, 701–718. doi:10.1016/j.cell.2009.02.009
Wang, Y., Liu, J., Huang, B., Xu, Y.-M., Li, J., Huang, L.-F., et al. (2015). Mechanism of alternative splicing and its regulation. Biomed. Rep. 3, 152–158. doi:10.3892/br.2014.407
Weatheritt, R. J., Sterne-Weiler, T., and Blencowe, B. J. (2016). The ribosome-engaged landscape of alternative splicing. Nat. Struct. Mol. Biol. 23, 1117–1123. doi:10.1038/nsmb.3317
Will, C. L., and Lührmann, R. (2011). Spliceosome structure and function. Cold Spring Harb. Perspect. Biol. 3, a003707. doi:10.1101/cshperspect.a003707
Wilusz, J. E., JnBaptiste, C. K., Lu, L. Y., Kuhn, C.-D., Joshua-Tor, L., and Sharp, P. A. (2012). A triple helix stabilizes the 3′ ends of long noncoding RNAs that lack poly(A) tails. Genes Dev. 26, 2392–2407. doi:10.1101/gad.204438.112
Xie, J., de Souza Alves, V., von der Haar, T., O’Keefe, L., Lenchine, R. V., Jensen, K. B., et al. (2019). Regulation of the elongation phase of protein synthesis enhances translation accuracy and modulates lifespan. Curr. Biol. 29, 737–749. doi:10.1016/j.cub.2019.01.029
Xiong, Y., and Eickbush, T. H. (1990). Origin and evolution of retroelements based upon their reverse transcriptase sequences. EMBO J. 9, 3353–3362. doi:10.1002/j.1460-2075.1990.tb07536.x
Yan, S., Deng, Y., Qiang, Y., Xi, Q., Liu, R., Yang, S., et al. (2015). SYF2 is upregulated in human epithelial ovarian cancer and promotes cell proliferation. Tumour Biol. 36, 4633–4642. doi:10.1007/s13277-015-3111-1
Zhang, S., Shi, W., Chen, Y., Xu, Z., Zhu, J., Zhang, T., et al. (2015). Overexpression of SYF2 correlates with enhanced cell growth and poor prognosis in human hepatocellular carcinoma. Mol. Cell Biochem. 410, 1–9. doi:10.1007/s11010-015-2533-9
Zhao, C., and Pyle, A. M. (2017). Structural insights into the mechanism of group II intron splicing. Trends Biochem. Sci. 42, 470–482. doi:10.1016/j.tibs.2017.03.007
Keywords: RNA, splicing, non-coding RNA, short non-coding RNA, RNA translational control, RNA viruses, RNA synthetic biology, ribozymes
Citation: Shirokikh NE, Jensen KB and Thakor N (2023) Editorial: RNA machines. Front. Genet. 14:1290420. doi: 10.3389/fgene.2023.1290420
Received: 07 September 2023; Accepted: 18 September 2023;
Published: 27 September 2023.
Edited and reviewed by:
William C. Cho, QEH, Hong Kong SAR, ChinaCopyright © 2023 Shirokikh, Jensen and Thakor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Nikolay E. Shirokikh, bmlrb2xheS5zaGlyb2tpa2hAYW51LmVkdS5hdQ==