The Emerging Role of lncRNA in the Regulation of the Endocrine Physiology

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Background

The percentage of the protein-coding genome of many eukaryotic organisms is proportionally small. In humans, protein-coding genes represent only 2% of the whole genome. However, a decade ago, other regulatory and functional units encoding long noncoding RNAs (lncRNAs) were discovered in the non-coding regions of the genome for all species. LncRNAs are defined as transcripts of more than 200 nucleotides without potential open reading frames for protein translation activity. With time and advanced technology, the number of lncRNA gene loci has grown exponentially. For instance, NONCODEv5 is a public database for the collection and annotation of lncRNA across 17 different species. So far, this web database has recorded a total of 548,640 transcripts spanning 354,855 lncRNA genes.
These lncRNA genes, like protein-coding genes, produce RNA transcriptional units. Despite not having protein translational capacity, these RNA transcripts from lncRNA genes are functional molecules. A myriad of functions for lncRNA in many cellular processes from gene imprinting, cell differentiation, growth, and responses to diverse stresses, stimuli and hormones, to key roles in the nervous, muscular, cardiovascular, adipose, haematopoietic, immune and especially endocrine systems and their associated pathologies have been reported. All these crucial tasks are executed by lncRNA through multiple functional mechanisms such as epigenetic modifier, transcriptional activator or repressor, scaffolds for proteins, decoys, miRNA sponge. Highlighting studies on the function of lncRNAs in the endocrine system is fundamental, as very little is known on their role in many important endocrine organs, including the pituitary, thyroid and parathyroid glands, and the hypothalamus.

Interestingly, in the recent past, not only their numbers but diversity in their functional mechanisms have also been expanded. This functional diversity of lncRNAs is not limited to RNA entities. Many of the lncRNA loci have their role in local gene regulation, but unexplored. For instance, not the RNA product of lncRNA, but the transcription of the lncRNA gene itself is important for the regulation of gene locus. The atypical list of functions of lncRNAs is continuously growing. The catalytic RNA molecules “ribozymes” are fascinating to researchers, yet very few have been identified. Recently, lncRNA containing catalytic ribozymes have also been reported, adding another intriguing functional property under its name. However, the field of lncRNA containing ribozymes and their role in endocrine physiology is still in its infancy.

The lncRNAs do not have the capability to code for proteins. However, more recently, micropeptides encoded from small open reading frames (ORFs) that lie within the lncRNA sequences are emerging as essential mediators of biological processes in health and disease. Moreover, in general, circRNAs are shaped out from pre-mRNA introns or exons but not limited, they have also been identified from long noncoding RNA genes. Therefore, lncRNA genes are also a source for circular RNA. It could also be possible that one of the functions of a lncRNA gene is to produce circular RNA, further increasing its functional role. The same phenomenon is true for microRNAs (miRNAs). Lnc-MIRHGs are usually referred to as lncRNAs genes that harbor miRNAs.
Lastly, alternative splicing of long noncoding RNAs produces several isoforms, many of which are not captured in genomic annotations. In addition, only highly expressed variants among annotated transcripts get the attention of researchers for further investigation. As could be the key to the functional diversity of lncRNAs, which is not well known.

The number and types of functional lncRNAs identified in the biological systems are constantly increasing, and an escalating number of these transcripts have been identified to be involved in the different endocrine pathways. Indeed, lncRNAs have critical roles in the development of endocrine cells and their expression is often regulated in response to hormones. Moreover, some SNPs in lncRNA have been linked with the pathogenesis of endocrine diseases as well as some endocrine cancers. Nevertheless, many questions still remain unanswered.
With this research topic, our goal is to collect the efforts of researchers on the emerging functional properties of lncRNAs, particularly in the endocrine systems of normal or cancer patients. Therefore, we aim to accept submissions of original research articles, case reports, reviews, mini-reviews, bioinformatics, and clinical studies relevant to the unique & under-studied roles of lncRNA. Themes of interest include, but are not limited to:

1. Regulatory roles of lncRNA gene loci including enhancer associated lncRNAs (e-lncRNA)

2. Ribozymes containing lncRNAs

3. lncRNA-encoded micropeptides

4. lncRNA-encoded circular RNAs

5. lncRNA-encoded microRNAs

6. alternative splicing of lncRNAs and spliced isoforms of lncRNAs

7. Bioinformatic analysis, pipelines, or curated databases covering unique properties of lncRNAs

Keywords: lncRNA, lncRNA loci, ribozyme, micropeptides, circular RNAs, microRNAs, alternative splicing, spliced isoforms

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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