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Published October 6, 2017 | Version v1
Journal article Open

YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs

Creators

  • 1. University of Chicago
  • 2. ShanghaiTech University
  • 3. Nanjing Medical University

Description

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.

Data availability

The following data sets were generated:

Ian A Roundtree Guan-Zheng Luo Chuan He (2015) N6-methyladenosine-Mediated Nuclear Export of Messenger RNA Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE74397). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74397

The following previously published data sets were used:

Wang X Lu Z Yue Y Han D Hon GC Ren B Pan T He C (2013) N6-methyladenosine-Mediated Nuclear Export of Messenger RNA Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE49339). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49339

Alarcon CR Goodarzi H Lee H Liu X Tavazoie S Tavazoie SF (2015) Nuclear HNRNPA2B1 HITS-CLIP and RNA-seq Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE70061). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70061

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Additional details

Identifiers

DOI
10.7554/eLife.31311
Other
oai:uchicago.tind.io:9935

Funding

National Institute of General Medical Sciences
F30GM117646
Howard Hughes Medical Institute
National Science Foundation
CHE-1048528
National Institute of General Medical Sciences
HG008688
National Institute of General Medical Sciences
GM113194
National Natural Science Foundation of China
31171377
National Natural Science Foundation of China
31471400

UChicago Information

Division(s)
Biological Sciences Division, Physical Sciences Division
Department(s)
Biochemistry and Molecular Biology, Chemistry
Center(s) or Institute(s)
Institute for Biophysical Dynamics