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PMID: 28106072 Published · ppublish English Journal Article

YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA.

Cell research ·Vol. 27 ·No. 3 ·2017-03-00 ·Pages 315-328

Shi H, Wang X, Lu Z, Zhao BS, Ma H, Hsu PJ, Liu C, He C

Abstract

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs), and plays important roles in cell differentiation and tissue development. It regulates multiple steps throughout the RNA life cycle including RNA processing, translation, and decay, via the recognition by selective binding proteins. In the cytoplasm, m6A binding protein YTHDF1 facilitates translation of m6A-modified mRNAs, and YTHDF2 accelerates the decay of m6A-modified transcripts. The biological function of YTHDF3, another cytoplasmic m6A binder of the YTH (YT521-B homology) domain family, remains unknown. Here, we report that YTHDF3 promotes protein synthesis in synergy with YTHDF1, and affects methylated mRNA decay mediated through YTHDF2. Cells deficient in all three YTHDF proteins experience the most dramatic accumulation of m6A-modified transcripts. These results indicate that together with YTHDF1 and YTHDF2, YTHDF3 plays critical roles to accelerate metabolism of m6A-modified mRNAs in the cytoplasm. All three YTHDF proteins may act in an integrated and cooperative manner to impact fundamental biological processes related to m6A RNA methylation.

MeSH Terms
Adenosine/analogs & derivatives,metabolism Base Sequence Cytosol/metabolism HeLa Cells Humans Models, Biological Protein Binding Protein Biosynthesis RNA/metabolism RNA Stability RNA-Binding Proteins/metabolism
Chemicals
RNA-Binding Proteins YTHDF1 protein, human YTHDF2 protein, human YTHDF3 protein, human RNA N-methyladenosine Adenosine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Shi Hailing
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. | Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Wang Xiao
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. | Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Lu Zhike
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. | Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Zhao Boxuan S
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. | Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Ma Honghui
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. | Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Hsu Phillip J
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. | Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA. | Committee on Immunology, The University of Chicago, Chicago, IL 60637, USA.
Liu Chang
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. | Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
He Chuan
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. | Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA. | Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
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Article Info
Journal
Cell research
Abbr.
Cell Res
ISSN
1748-7838
DOI
10.1038/cr.2017.15
Published
2017-03-00
Epub
2017-00-20
Pages
315-328
Language
English
Region
England
NLM ID
9425763
PMCID
PMC5339834
Subset
IM
Grants
NIGMS NIH HHS · R01 GM071440 · United States
NIGMS NIH HHS · R01 GM113194 · United States
External Links
PubMed source DOI: 10.1038/cr.2017.15 PMC Full Text View journal details
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