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Elife. 2017 Oct 6;6. pii: e31311. doi: 10.7554/eLife.31311.

YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs.

Roundtree IA1,2,3,4, Luo GZ1,2,3, Zhang Z1,2,3, Wang X1,2,3, Zhou T5, Cui Y6, Sha J6, Huang X5, Guerrero L1,2,3, Xie P1,2,3, He E1,2,3, Shen B6, He C1,2,3.

Author information

1
Department of Chemistry, University of Chicago, Chicago, United States.
2
Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, University of Chicago, Chicago, United States.
3
Howard Hughes Medical Institute, University of Chicago, Chicago, United States.
4
University of Chicago Medical Scientist Training Program, Chicago, United States.
5
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
6
Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

Abstract

N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic messenger RNA (mRNA) and plays critical roles in RNA biology. The function of this modification is mediated by m6A-selective 'reader' proteins of the YTH family, which incorporate m6A-modified mRNAs into pathways of RNA metabolism. Here, we show that the m6A-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells. Knockdown of YTHDC1 results in an extended residence time for nuclear m6A-containing mRNA, with an accumulation of transcripts in the nucleus and accompanying depletion within the cytoplasm. YTHDC1 interacts with the splicing factor and nuclear export adaptor protein SRSF3, and facilitates RNA binding to both SRSF3 and NXF1. This role for YTHDC1 expands the potential utility of chemical modification of mRNA, and supports an emerging paradigm of m6A as a distinct biochemical entity for selective processing and metabolism of mammalian mRNAs.

KEYWORDS:

RNA modification; RNA processing; biochemistry; cell biology; gene regulation; human; mRNA export

PMID:
28984244
PMCID:
PMC5648532
DOI:
10.7554/eLife.31311
[Indexed for MEDLINE]
Free PMC Article

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