Abstract
N6-methyladenosine (m6A) is the most abundant internal modification in 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.
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Funding
National Institute of General Medical Sciences (F30GM117646)
- Ian A Roundtree
Howard Hughes Medical Institute
- Ian A Roundtree
- Guan-Zheng Luo
- Zijie Zhang
- Xiao Wang
- Chuan He
National Science Foundation (CHE-1048528)
- Ian A Roundtree
- Guan-Zheng Luo
- Zijie Zhang
- Xiao Wang
- Laura Guerrero
- Phil Xie
- Emily He
- Chuan He
National Institute of General Medical Sciences (HG008688)
- Chuan He
National Institute of General Medical Sciences (GM113194)
- Chuan He
National Natural Science Foundation of China (31171377)
- Xingxu Huang
National Natural Science Foundation of China (31471400)
- Xingxu Huang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Nick J Proudfoot, University of Oxford, United Kingdom
Version history
- Received: August 17, 2017
- Accepted: October 4, 2017
- Accepted Manuscript published: October 6, 2017 (version 1)
- Version of Record published: October 19, 2017 (version 2)
Copyright
© 2017, Roundtree et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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YTHDC1 Mediates Nuclear Export of N6-methyladenosine Methylated mRNAs
eLife 6:e31311.
https://doi.org/10.7554/eLife.31311
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