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Review
. 2021 Oct 15;18(sup1):117-127.
doi: 10.1080/15476286.2021.1950993. Epub 2021 Jul 21.

RNA 5-methylcytosine modification and its emerging role as an epitranscriptomic mark

Yaqi Gao  1 , Jingyuan Fang  1
Affiliations
Review

RNA 5-methylcytosine modification and its emerging role as an epitranscriptomic mark

Yaqi Gao et al. RNA Biol. .

Abstract

5-methylcytosine (m5C) is identified as an abundant and conserved modification in various RNAs, including tRNAs, mRNAs, rRNAs, and other non-coding RNAs. The application of high-throughput sequencing and mass spectrometry allowed for the detection of m5C at a single-nucleotide resolution and at a global abundance separately; this contributes to a better understanding of m5C modification and its biological functions. m5C modification plays critical roles in diverse aspects of RNA processing, including tRNA stability, rRNA assembly, and mRNA translation. Notably, altered m5C modifications and mutated RNA m5C methyltransferases are associated with diverse pathological processes, such as nervous system disorders and cancers. This review may provide new sights of molecular mechanism and functional importance of m5C modification.

Keywords: 5-methylcytosine (m5C); RNA m5C methyltransferase; RNA methylation; epitranscriptome.

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Conflict of interest statement

The authors have declared no competing interests.

Figures

Figure 1.
Figure 1.
Detection methods of RNA m5C. RNA-BisSeq relied on bisulphite conversion and high-throughput sequencing. Immunoprecipitation-based detection methods are based on specific antibodies targeting m5C or enzymes, which include MeRIP-seq, 5-azaIP and miCLIP. Third generation sequencing directly detects RNA sequences and modifications. LC-MS/MS combines high pressure liquid chromatography (HPLC) separation and mass spectrometry (MS) measurement, providing a global abundance of RNA m5C modification
Figure 2.
Figure 2.
Distribution patterns and roles of m5C in mRNA. m5C is distributed among all the regions in mRNA, mainly enriched within 3ʹUTR and around translation start sites. m5C plays various roles in mRNA metabolism, including mRNA stability and mRNA nuclear-cytoplasmic shuttling and mRNA translation
Figure 3.
Figure 3.
m5C in tRNA metabolism and its association with stress. Loss of NSUN2-mediated m5C in tRNA increases the angiogenin-mediated tRNAs cleavage, results in an accumulation of tRNA-derived small RNA fragments, reduces protein translation rates and thus activates stress response
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This work was supported by the National Natural Science Foundation of China [81421001, 81830081].