RNA modification occurs in all living organisms, and is one of the most evolutionarily conserved properties of RNAs. It can affect the activity, localization as well as stability of RNAs, and has been linked with human diseases.
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More than 100 types of RNA modifications have been described so far, recent studies have revealed they are abundant in mRNAs and in regulatory non-coding RNAs (ncRNAs, e.g. lncRNAs, miRNAs, snoRNAs) as well as in tRNAs, rRNAs and snRNAs.
RNA Modification Technologies
To determine the transcriptome-wide landscape of RNA modifications, recently many studies have developed high-throughput modification sequencing methods to identify diverse post-transcriptional modifications of RNA molecules. Application of these methods (MeRIP-seq, m6A-seq, methylation-iCLIP, m6A-CLIP, Pseudo-seq, Ψ-seq, CeU-seq, Aza-IP, RiboMeth-seq) has identified various modifications (e.g. pseudouridine, m6A, m5C, 2′-O-Me) within coding genes and non-coding genes (e.g. lncRNAs, microRNAs) at single nucleotide or very high resolution. A novel database, RMBase (http://mirlab.sysu.edu.cn/rmbase/), has provide various web interfaces to show all RNA modification sites identified from above-mentioned sequencing technologies.
RNA Modification Functions
Recently, functional experiments have revealed many novel functional roles of RNA modifications. For example, m6A has been predicted to affect protein translation and localization, mRNA stability, alternative polyA choice and stem cell pluripotency. Pseudouridylation of nonsense codons suppresses translation termination both in vitro and in vivo, suggesting that RNA modification may provide a new way to expand the genetic code. Importantly, many modification enzymes are dysregulated and genetically mutated in many disease types. For example, genetic mutations in pseudouridine synthases cause mitochondrial myopathy, sideroblastic anemia (MLASA) and dyskeratosis congenital.