Dynamic transcriptomic m⁵C and its regulatory role in RNA processing

Abstract

RNA 5‐methylcytosine (m5C) is a prevalent RNA modification in multiple RNA species, including messenger RNAs (mRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), and noncoding RNAs (ncRNAs), and broadly distributed from archaea, prokaryotes to eukaryotes. The multiple detecting techniques of m5C have been developed, such as m5C‐RIP‐seq, miCLIP‐seq, AZA‐IP‐seq, RNA‐BisSeq, TAWO‐seq, and Nanopore sequencing. These high‐throughput techniques, combined with corresponding analysis pipeline, provide a precise m5C landscape contributing to the deciphering of its biological functions. The m5C modification is distributed along with mRNA and enriched around 5′UTR and 3′UTR, and conserved in tRNAs and rRNAs. It is dynamically regulated by its related enzymes, including methyltransferases (NSUN, DNMT, and TRDMT family members), demethylases (TET families and ALKBH1), and binding proteins (ALYREF and YBX1). So far, accumulative studies have revealed that m5C participates in a variety of RNA metabolism, including mRNA export, RNA stability, and translation. Depletion of m5C modification in the organism could cause dysfunction of mitochondria, drawback of stress response, frustration of gametogenesis and embryogenesis, abnormality of neuro and brain development, and has been implicated in cell migration and tumorigenesis. In this review, we provide a comprehensive summary of dynamic regulatory elements of RNA m5C, including methyltransferases (writers), demethylases (erasers), and binding proteins (readers). We also summarized the related detecting technologies and biological functions of the RNA 5‐methylcytosine, and provided future perspectives in m5C research. This article is categorized under: RNA Processing > RNA Editing and Modification

Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 and ALYREF as new candidate risk genes

“…The RNA-binding protein ALYREF plays a key role in nuclear export through binding to the 5’ and the 3’ regions of mRNA 76,77 . It acts as an RNA 5-methylcytosine (m 5 C) adaptor to regulate the m 5 C modification 78,79 . Disruption of ALYREF could affect the m 5 C modification, resulting in abnormal cell proliferation and migration 79 .…”

“…It acts as an RNA 5-methylcytosine (m 5 C) adaptor to regulate the m 5 C modification 78,79 . Disruption of ALYREF could affect the m 5 C modification, resulting in abnormal cell proliferation and migration 79 . Previous studies 50 identified several RNA binding proteins (RBPs) playing essential roles in autism and congenital birth defects including CHD.…”

Epi‐miRNAs: Modern mediators of methylation status in human cancers

“…Yang, Hu, et al, 2020). Apart from m6A, 5-methylcytosine (m5C), N1-methyladenosine (m1A) and 7-methylguanosine (m7G) have emerged also as important epitranscriptomic modifications (Chen et al, 2021;Hoernes & Erlacher, 2017;Trixl & Lusser, 2019). Imprinting of m5C is catalyzed by NSUN family and DNMT2 (Liu et al, 2017), while ALYREF and YBX1 represent the only acknowledged m5C readers, encompassing pivotal roles in mRNA nuclear export and stability, respectively (Wiener & Schwartz, 2021).…”

Long Non-Coding RNA Epigenetics

“…Therefore, this method often requires additional confirmation with the aforementioned direct methods used for the detection of m 6 A modifications—MeRIP and miCLIP. They differ in the application of m 5 C-specific antibodies [ 136 ].…”