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Article Dans Une Revue Nucleic Acids Research Année : 2021

A comprehensive review of m6A/m6Am RNA methyltransferase structures

Stephanie Oerum
Marjorie Catala
Carine Tisné

Résumé

Abstract Gene expression is regulated at many levels including co- or post-transcriptionally, where chemical modifications are added to RNA on riboses and bases. Expression control via RNA modifications has been termed ‘epitranscriptomics’ to keep with the related ‘epigenomics’ for DNA modification. One such RNA modification is the N6-methylation found on adenosine (m6A) and 2′-O-methyladenosine (m6Am) in most types of RNA. The N6-methylation can affect the fold, stability, degradation and cellular interaction(s) of the modified RNA, implicating it in processes such as splicing, translation, export and decay. The multiple roles played by this modification explains why m6A misregulation is connected to multiple human cancers. The m6A/m6Am writer enzymes are RNA methyltransferases (MTases). Structures are available for functionally characterized m6A RNA MTases from human (m6A mRNA, m6A snRNA, m6A rRNA and m6Am mRNA MTases), zebrafish (m6Am mRNA MTase) and bacteria (m6A rRNA MTase). For each of these MTases, we describe their overall domain organization, the active site architecture and the substrate binding. We identify areas that remain to be investigated, propose yet unexplored routes for structural characterization of MTase:substrate complexes, and highlight common structural elements that should be described for future m6A/m6Am RNA MTase structures.

Dates et versions

hal-03544547 , version 1 (26-01-2022)

Identifiants

Citer

Stephanie Oerum, Vincent Meynier, Marjorie Catala, Carine Tisné. A comprehensive review of m6A/m6Am RNA methyltransferase structures. Nucleic Acids Research, 2021, 49 (13), pp.7239-7255. ⟨10.1093/nar/gkab378⟩. ⟨hal-03544547⟩
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