N 6 -methyladenosine (m 6 A) recruits and repels proteins to regulate mRNA homeostasis.

Autor: Edupuganti RR; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., Geiger S; Center for Integrated Protein Science at the Fakultät für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Munich, Germany., Lindeboom RGH; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., Shi H; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA., Hsu PJ; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA., Lu Z; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA., Wang SY; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., Baltissen MPA; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., Jansen PWTC; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., Rossa M; Center for Integrated Protein Science at the Fakultät für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Munich, Germany., Müller M; Center for Integrated Protein Science at the Fakultät für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Munich, Germany., Stunnenberg HG; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., He C; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA., Carell T; Center for Integrated Protein Science at the Fakultät für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Munich, Germany., Vermeulen M; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2017 Oct; Vol. 24 (10), pp. 870-878. Date of Electronic Publication: 2017 Sep 04.
DOI: 10.1038/nsmb.3462
Abstrakt: RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N 6 -methyladenosine (m 6 A), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to m 6 A to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of m 6 A interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by m 6 A and positively regulates mRNA stability in an m 6 A-regulated manner. Furthermore, we identified FMR1 as a sequence-context-dependent m 6 A reader, thus revealing a connection between an mRNA modification and an autism spectrum disorder. Collectively, our data represent a rich resource and shed further light on the complex interplay among m 6 A, m 6 A interactors and mRNA homeostasis.
Databáze: MEDLINE
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