“…Moreover, knock‐down of ALYREF in HeLa cells resulted in increased nuclear retention of m 5 C‐modified mRNA which could be rescued by expression of wild‐type ALYREF but not of a mutant version that was unable to bind m 5 C. In contrast, non‐m 5 C bearing mRNA showed no nuclear export defects upon ALYREF knockdown (Yang et al, ). Thus, ALYREF appears to be a bona fide m 5 C “reader” protein with the ability to regulate mRNA fate dependent on its m 5 C status, similar to what has been shown for other proteins in the context of the m 6 A modification (Dominissini & Rechavi, ).…”
Section: ‐Methylcytosine In Abundant Rna Speciessupporting
It is a well‐known fact that RNA is the target of a plethora of modifications which currently amount to over a hundred. The vast majority of these modifications was observed in the two most abundant classes of RNA, rRNA and tRNA. With the recent advance in mapping technologies, modifications have been discovered also in mRNA and in less abundant non‐coding RNA species. These developments have sparked renewed interest in elucidating the nature and functions of those “epitransciptomic” modifications in RNA. N6‐methyladenosine (m6A) is the best understood and most frequent mark of mRNA with demonstrated functions ranging from pre‐mRNA processing, translation, miRNA biogenesis to mRNA decay. By contrast, much less research has been conducted on 5‐methylcytosine (m5C), which was detected in tRNAs and rRNAs and more recently in poly(A)RNAs. In this review, we discuss recent developments in the discovery of m5C RNA methylomes, the functions of m5C as well as the proteins installing, translating and manipulating this modification. Although our knowledge about m5C in RNA transcripts is just beginning to consolidate, it has become clear that cytosine methylation represents a powerful mechanistic strategy to regulate cellular processes on an epitranscriptomic level.
This article is categorized under:
RNA Processing > RNA Editing and Modification
RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA Processing > tRNA Processing
RNA Turnover and Surveillance > Regulation of RNA Stability
“…Moreover, knock‐down of ALYREF in HeLa cells resulted in increased nuclear retention of m 5 C‐modified mRNA which could be rescued by expression of wild‐type ALYREF but not of a mutant version that was unable to bind m 5 C. In contrast, non‐m 5 C bearing mRNA showed no nuclear export defects upon ALYREF knockdown (Yang et al, ). Thus, ALYREF appears to be a bona fide m 5 C “reader” protein with the ability to regulate mRNA fate dependent on its m 5 C status, similar to what has been shown for other proteins in the context of the m 6 A modification (Dominissini & Rechavi, ).…”
Section: ‐Methylcytosine In Abundant Rna Speciessupporting
It is a well‐known fact that RNA is the target of a plethora of modifications which currently amount to over a hundred. The vast majority of these modifications was observed in the two most abundant classes of RNA, rRNA and tRNA. With the recent advance in mapping technologies, modifications have been discovered also in mRNA and in less abundant non‐coding RNA species. These developments have sparked renewed interest in elucidating the nature and functions of those “epitransciptomic” modifications in RNA. N6‐methyladenosine (m6A) is the best understood and most frequent mark of mRNA with demonstrated functions ranging from pre‐mRNA processing, translation, miRNA biogenesis to mRNA decay. By contrast, much less research has been conducted on 5‐methylcytosine (m5C), which was detected in tRNAs and rRNAs and more recently in poly(A)RNAs. In this review, we discuss recent developments in the discovery of m5C RNA methylomes, the functions of m5C as well as the proteins installing, translating and manipulating this modification. Although our knowledge about m5C in RNA transcripts is just beginning to consolidate, it has become clear that cytosine methylation represents a powerful mechanistic strategy to regulate cellular processes on an epitranscriptomic level.
This article is categorized under:
RNA Processing > RNA Editing and Modification
RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA Processing > tRNA Processing
RNA Turnover and Surveillance > Regulation of RNA Stability
In this review we explore the regulation of mRNA cap formation and its impact on mammalian cells. The mRNA cap is a highly methylated modification of the 5′ end of RNA pol II-transcribed RNA. It protects RNA from degradation, recruits complexes involved in RNA processing, export and translation initiation, and marks cellular mRNA as “self” to avoid recognition by the innate immune system. The mRNA cap can be viewed as a unique mark which selects RNA pol II transcripts for specific processing and translation. Over recent years, examples of regulation of mRNA cap formation have emerged, induced by oncogenes, developmental pathways and during the cell cycle. These signalling pathways regulate the rate and extent of mRNA cap formation, resulting in changes in gene expression, cell physiology and cell function.
“…Moreover, m 5 C epigenetic modification plays a significant role in eukaryotic biological functions such as nuclear export regulation and protein transcription modulation (Squires et al, 2012;Flores et al, 2017;Trixl and Lusser, 2019). Additionally, several studies have demonstrated that mRNA modification by the epitranscriptome marker m 5 C constituted an integral part of gene regulatory networks in both mammals and plants (Amort et al, 2017;Cui et al, 2017;Dominissini and Rechavi, 2017).…”
Epigenetic processes including RNA methylation, post-translational modifications, and non-coding RNA expression have been associated with the heritable risks of systemic lupus erythematosus (SLE). In this study, we aimed to explore the dysregulated expression of 5-methylcytosine (m 5 C) in CD4 + T cells from patients with SLE and the potential function of affected mRNAs in SLE pathogenesis. mRNA methylation profiles were ascertained through chromatography-coupled triple quadrupole mass spectrometry in CD4 + T cells from two pools of patients with SLE exhibiting stable activity, two pools with moderate-to-major activity, and two pools of healthy controls (HCs). Simultaneously, mRNA methylation profiles and expression profiling were performed using RNA-Bis-Seq and RNA-Seq, respectively. Integrated mRNA methylation and mRNA expression bioinformatics analysis was comprehensively performed. mRNA methyltransferase NSUN2 expression was validated in CD4 + T cells from 27 patients with SLE and 28 HCs using real-time polymerase chain reaction and western blot analyses. Hypomethylated-mRNA profiles of NSUN2-knockdown HeLa cells and of CD4 + T cells of patients with SLE were jointly analyzed using bioinformatics. Eleven methylation modifications (including elevated Am, 3 OMeA, m 1 A, and m 6 A and decreased , m 3 C, m 1 G, m 5 U, and t 6 A levels) were detected in CD4 + T cells of patients with SLE. Additionally, decreased m 5 C levels, albeit increased number of m 5 C-containing mRNAs, were observed in CD4 + T cells of patients with SLE compared with that in CD4 + T cells of HCs. m 5 C site distribution in mRNA transcripts was highly conserved and enriched in mRNA translation initiation sites. In particular, hypermethylated m 5 C or/and significantly up-regulated genes in SLE were significantly involved in immune-related and inflammatory pathways, including immune system,
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
