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RNA methylation in nuclear pre‐mRNA processing

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Eukaryotic RNA can carry more than 100 different types of chemical modifications. Early studies have been focused on modifications of highly abundant RNA, such as ribosomal RNA and transfer RNA, but recent technical advances have made it possible to also study messenger RNA (mRNA). Subsequently, mRNA modifications, namely methylation, have emerged as key players in eukaryotic gene expression regulation. The most abundant and widely studied internal mRNA modification is N6‐methyladenosine (m6A), but the list of mRNA chemical modifications continues to grow as fast as interest in this field. Over the past decade, transcriptome‐wide studies combined with advanced biochemistry and the discovery of methylation writers, readers, and erasers revealed roles for mRNA methylation in the regulation of nearly every aspect of the mRNA life cycle and in diverse cellular, developmental, and disease processes. Although large parts of mRNA function are linked to its cytoplasmic stability and regulation of its translation, a number of studies have begun to provide evidence for methylation‐regulated nuclear processes. In this review, we summarize the recent advances in RNA methylation research and highlight how these new findings have contributed to our understanding of methylation‐dependent RNA processing in the nucleus. This article is categorized under: RNA Processing > RNA Editing and Modification RNA Processing > Splicing Regulation/Alternative Splicing RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
A schematic view of the structure and localization of methylated nucleosides in eukaryotic mRNA. The bold line represents the coding sequence, and the thin lines are 5′ and 3′ untranslated regions (UTRs). Abbreviations: m7G, 7‐methylguanosine; m6Am, N6,2′‐O‐methyaldenosine; Nm, 2′‐O‐ribose methylation; m1A, N1‐methyladenosine; m6A, N6‐methyladenosine; m5C, 5‐methylcytosine; m3C, 3‐methylcytosine
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A schematic view of the role of the m6A methylation/demethylation pathway in nuclear pre‐mRNA processing. Writers, erasers, and known readers of m6A that play a role in splicing, 3′ end processing, and nuclear mRNA export are shown
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The chemical formula of the eukaryotic mRNA 5′‐m7G cap structure with the two downstream nucleotides included. Red: stable methyl group that forms the “Cap 0” structure (m7GpppN). Green: stable methyl groups that form the “Cap 1” (m7GpppNm) and “Cap 2” (m7GpppNmNm) structures. Blue: if the first nucleotide of the mRNA is adenosine, it can be further methylated at the N6 position of the base (m7Gpppm6Am). The enzymes responsible for methylation/demethylation of the specific groups are depicted
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RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition
RNA Processing > Splicing Regulation/Alternative Splicing
RNA Processing > RNA Editing and Modification

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