About this Research Topic
RNA modifications are collectively known as “epitranscriptomic modifications”. With the recent advancement in technologies over 170 distinct RNA chemical modifications have been identified so far, in both coding and non-coding RNAs. Among these, some of the most extensively studied RNA modifications include N6-methyladenosine (m6A) found on eukaryotic mRNA, 5-methylcytosine(m5C) found on rRNA, tRNA, ncRNA and mRNA, Pseudouridine(ψ) observed in tRNAs, rRNAs, and snRNA, N1-methyladenosine (m1A) predominantly found on tRNA and rRNA and N4-acetylcytidine (ac4C) detected in tRNA, rRNA, and recently on mRNA. RNA modifications regulate various biological processes including RNA stability, translation, splicing, and RNA export from the nucleus to cytoplasm. Recent development of mRNA vaccines to combat fatal SARS-CoV2 infection has opened several new possibilities to diagnose, control and treat many other diseases such as cancer, diabetes, cardiovascular complications and many infectious diseases using RNA modifications.
There are two main approaches like (i) next generation sequencing (NGS) and (ii) mass spectrometry (MS) by virtue of which RNA modifications can be identified and quantified. The pitfalls in NGS and MS methods include but not limited to non-reproducibility, high costs and non-availability of antibodies against modification or even if antibodies are available, they lack specificity especially in the case of m6A and m6Am. The better technical advancements with affordable costs are much needed to explore RNA modifications for RNA therapeutics. So far more than 17 RNA based drugs are approved by FDA and 222 are under clinical trials. Among approved therapies, mRNA, small interfering RNA and antisense oligos are commonly exploited. As RNA modifications are highly context dependent and catalysed on all types of RNA, future studies should focus on discovering personalized medicine with high specificity and less off-target effects to treat various human diseases including:
• RNA epitranscriptomics
• Chemical composition of RNA modifications
• Functions of RNA modifications
• RNA therapeutics
• Role of RNA modifications in developing RNA therapeutics
• Technical advancements in studying the RNA modifications
• Crosstalk between epitranscriptomics markers
There are two main approaches like (i) next generation sequencing (NGS) and (ii) mass spectrometry (MS) by virtue of which RNA modifications can be identified and quantified. The pitfalls in NGS and MS methods include but not limited to non-reproducibility, high costs and non-availability of antibodies against modification or even if antibodies are available, they lack specificity especially in the case of m6A and m6Am. The better technical advancements with affordable costs are much needed to explore RNA modifications for RNA therapeutics. So far more than 17 RNA based drugs are approved by FDA and 222 are under clinical trials. Among approved therapies, mRNA, small interfering RNA and antisense oligos are commonly exploited. As RNA modifications are highly context dependent and catalysed on all types of RNA, future studies should focus on discovering personalized medicine with high specificity and less off-target effects to treat various human diseases including:
• RNA epitranscriptomics
• Chemical composition of RNA modifications
• Functions of RNA modifications
• RNA therapeutics
• Role of RNA modifications in developing RNA therapeutics
• Technical advancements in studying the RNA modifications
• Crosstalk between epitranscriptomics markers
Keywords: Epitranscriptomics, RNA modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), Pseudouridine (ψ), N1-methyladenosine (m1A), N4-acetylcytidine (ac4C), RNA stability, RNA splicing, RNA translation, RNA export, RNA therapeutics, mRNA vaccines
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