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PMID: 28869609 Published · ppublish English Journal Article

N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis.

Nature structural & molecular biology ·Vol. 24 ·No. 10 ·2017-10-00 ·Pages 870-878

Edupuganti RR, Geiger S, Lindeboom RGH, Shi H, Hsu PJ, Lu Z, Wang SY, Baltissen MPA, Jansen PWTC, Rossa M, Müller M, Stunnenberg HG, He C, Carell T, Vermeulen M

Abstract

RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N6-methyladenosine (m6A), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to m6A to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of m6A interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by m6A and positively regulates mRNA stability in an m6A-regulated manner. Furthermore, we identified FMR1 as a sequence-context-dependent m6A 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 m6A, m6A interactors and mRNA homeostasis.

MeSH Terms
Adenosine/analogs & derivatives,metabolism Animals Cell Line Homeostasis Humans Mass Spectrometry Protein Binding Proteins/metabolism RNA, Messenger/metabolism
Chemicals
Proteins RNA, Messenger N-methyladenosine Adenosine
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Edupuganti Raghu R
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.
Geiger Simon
Center for Integrated Protein Science at the Fakultät für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Munich, Germany.
Lindeboom Rik G H
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.
Shi Hailing ORCID
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 Phillip J
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 Zhike
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 Shuang-Yin
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.
Baltissen Marijke P A
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.
Jansen Pascal W T C
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.
Rossa Martin
Center for Integrated Protein Science at the Fakultät für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Munich, Germany.
Müller Markus
Center for Integrated Protein Science at the Fakultät für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Munich, Germany.
Stunnenberg Hendrik G
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.
He Chuan
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 Thomas ORCID
Center for Integrated Protein Science at the Fakultät für Chemie und Pharmazie, Ludwig-Maximilians-Universität München, Munich, Germany.
Vermeulen Michiel ORCID
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.3462
Published
2017-10-00
Epub
2017-00-04
Pages
870-878
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC5725193
Subset
IM
Grants
NHGRI NIH HHS · R01 HG008688 · United States
External Links
PubMed source DOI: 10.1038/nsmb.3462 PMC Full Text View journal details
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