Post-transcriptional regulation by cytosine-5 methylation of RNA

Abstract

The recent advent of high-throughput sequencing technologies coupled with RNA modifications detection methods has allowed the detection of RNA modifications at single nucleotide resolution giving a more comprehensive landscape of post-transcriptional gene regulation pathways. In this review, we focus on the occurrence of 5-methylcytosine (m 5 C) in the transcriptome. We summarise the main findings of the molecular role in posttranscriptional regulation that governs m 5 C deposition in RNAs. Functionally, m 5 C deposition can regulate several cellular and physiological processes including development, differentiation and survival to stress stimuli. Despite many aspects concerning m 5 C deposition in RNA, such as position or sequence context, and the fact that many readers and erasers still remain elusive, the overall recent findings indicate that RNA cytosine methylation is a powerful mechanism to post-transcriptionally regulate physiological processes. In addition, mutations in RNA cytosine-5 methyltransferases are associated to pathological processes ranging from neurological syndromes to cancer.

Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

“…With the advances in RNA m 5 C detection techniques, including bisulfite sequencing, m 5 C RNA immunoprecipitation sequencing (m 5 C-RIP-seq), 5-AZAcytidinemediated RNA immunoprecipitation sequencing (Aza-IP-seq) and methylation-individual nucleotide resolution crosslinking immunoprecipitation sequencing (miCLIPseq), over 10,000 potential sites of m 5 C modification were detected within the whole human transcriptome [7], and the existence of m 5 C was found in diverse RNA species from various organisms, not only in ribosomal RNA (rRNA), messenger RNA (mRNA) and transfer RNA (tRNA) but also in viral RNA, vault RNA, small nuclear RNA, small nucleolar RNA, pseudogenes, natural antisense transcripts, enhancer RNA, long noncoding RNA (lncRNA) and microRNA (miRNA) [8][9][10][11][12][13][14][15]. The distribution of m 5 C differs among different organisms, as it has been common to find m 5 C methylation substrates in the tRNA and mRNA of eukaryotes and archaea, while no m 5 C methylation substrates have been detected in bacteria [16].…”

“…Finally, by discussing the role of m 5 C in tumorigenesis and cancer progression, we propose m 5 C-based approaches for cancer diagnosis, prognosis and clinical treatment. Although some statements in our study may briefly touch on other reviews [8,16,25], which discussed the detection methods and biological functions of RNA m 5 C methylation in depth, we focus on literature published in the past five years and are the first to thoroughly discuss the clinical prospect of RNA m 5 C in cancer treatment.…”

Identification of RNA: 5-Methylcytosine Methyltransferases-Related Signature for Predicting Prognosis in Glioma

“…This post-transcriptional modification of m 5 C has been detected in most RNA species, including messenger RNAs (mRNA), mitochondrial ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), enhancer RNAs (eRNAs), cytoplasmic RNAs, and non-coding RNAs (12)(13)(14)(15). m 5 C methylation of RNA is catalyzed by the NOL1/NOP2/sun domain RNA methyltransferase family and the DNA methyltransferase homolog TRDMT1 (formerly known as the DNA methyltransferase member DNMT2) in eukaryotes, but the function of the binding proteins and demethylases remains unclear, while there is evidence to suggest that YBX1 might be the binding protein for m 5 C (11,(15)(16)(17)(18)(19)(20). The cellular functions and modifications of these enzymes contribute to our understanding of the mechanism of m 5 C involvement in epigenetic inheritance related to various diseases, including tumors.…”

RNA modifications in the regulation of hematopoiesis and leukemogenesis

“…rRNA, mRNA等 [67] . 已报道的m 5 C甲基转移酶包括 DNMT2 [68] 和NOL1/NOP2/sun 1-7(NSUN1-7)家族成 员 [69] , 其中DNMT2介导Asp, Gly, Val tRNA C38的 m 5 C修饰, 其作用与翻译的准确性有关, 影响造血干祖 细胞的数量和分化能力 [68] . 5-氮杂胞苷(5-azacitidine, [39,40] .…”