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      Where, when and how: context-dependent functions of RNA methylation writers, readers, and erasers

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          Abstract

          Cellular RNAs are naturally decorated with a variety of chemical modifications. The structural diversity of the modified nucleosides provides regulatory potential to sort groups of RNAs for organized metabolism and functions, thus affecting gene expression. Recent years have witnessed a burst of interest in and understanding of RNA modification biology, thanks to the emerging transcriptome-wide sequencing methods for mapping modified sites, highly-sensitive mass spectrometry for precise modification detection and quantification, and extensive characterization of the modification “effectors”, including enzymes (“writers” and “erasers”) that alter the modification level and binding proteins (“readers”) that recognize the chemical marks. However, challenges remain due to the vast heterogeneity in expression abundance of different RNA species, further complicated by divergent cell-type-specific and tissue-specific expression and localization of the effectors as well as modifications. In this review, we highlight recent progress in understanding the function of N 6-methyladenosine (m 6A), the most abundant internal mark on eukaryotic messenger RNA (mRNA), in light of the specific biological contexts of m 6A effectors. We emphasize the importance of context for RNA modification regulation and function.

          eTOC Blurb

          RNA N 6-methyladenosine (m 6A) has emerged as a multifaceted controller for gene expression regulation, mediated through its effector proteins—writers, readers, and erasers. Shi et al. review recent advances in the mechanistic understandings of m 6A effectors in various biological systems and cellular responses, emphasizing cellular and molecular contexts as important determinants of RNA modification functions.

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          Author and article information

          Journal
          9802571
          20730
          Mol Cell
          Mol. Cell
          Molecular cell
          1097-2765
          1097-4164
          8 May 2019
          16 May 2019
          16 May 2020
          : 74
          : 4
          : 640-650
          Affiliations
          [1 ]Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA
          [2 ]Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA
          [3 ]These authors contributed equally
          Author notes
          [* ]Correspondence and Lead Contact: chuanhe@ 123456uchicago.edu
          Article
          PMC6527355 PMC6527355 6527355 nihpa1528814
          10.1016/j.molcel.2019.04.025
          6527355
          31100245
          52921177-ab4b-4bb8-9018-4135cab4a610
          History
          Categories
          Article

          Context-dependent functions,FTO,YTHDF proteins,METTL3/14,Gene expression regulation, N 6-methyladenosine (m6A),Epitranscriptome,RNA modifications

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