The m6A-methylase complex recruits TREX and regulates mRNA export

Abstract

N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA. This modification has previously been shown to alter the export kinetics for mRNAs though the molecular details surrounding this phenomenon remain poorly understood. Recruitment of the TREX mRNA export complex to mRNA is driven by transcription, 5' capping and pre-mRNA splicing. Here we identify a fourth mechanism in human cells driving the association of TREX with mRNA involving the m6A methylase complex. We show that the m6A complex recruits TREX to m6A modified mRNAs and this process is essential for their efficient export. TREX also stimulates recruitment of the m6A reader protein YTHDC1 to the mRNA and the m6A complex influences the interaction of TREX with YTHDC1. Together our studies reveal a key role for TREX in the export of m6A modified mRNAs.

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Item Type:	Article
Authors/Creators:	Lesbirel, S. Viphakone, N. Parker, M. Parker, J. Heath, C. Sudbery, I. https://orcid.org/0000-0002-5038-0190 Wilson, S.A. https://orcid.org/0000-0003-3073-258X
Copyright, Publisher and Additional Information:	© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Published: 14 September 2018 Published (online): 14 September 2018 Accepted: 4 September 2018
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	19 Sep 2018 15:21
Last Modified:	21 Sep 2018 07:36
Published Version:	https://doi.org/10.1038/s41598-018-32310-8
Status:	Published
Publisher:	Nature Publishing Group
Refereed:	Yes
Identification Number:	10.1038/s41598-018-32310-8
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:135762

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The m6A-methylase complex recruits TREX and regulates mRNA export

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