The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci
Abstract
UPF1 is an RNA helicase that is required for efficient nonsense-mediated mRNA decay (NMD) in eukaryotes, and the predominant view is that UPF1 mainly operates on the 3'UTRs of mRNAs that are directed for NMD in the cytoplasm. Here we offer evidence, obtained from Drosophila, that UPF1 constantly moves between the nucleus and cytoplasm by a mechanism that requires its RNA helicase activity. UPF1 is associated, genome-wide, with nascent RNAs at most of the active Pol II transcription sites and at some Pol III-transcribed genes, as demonstrated microscopically on the polytene chromosomes of salivary glands and by ChIP-seq analysis in S2 cells. Intron recognition seems to interfere with association and translocation of UPF1 on nascent pre-mRNAs, and cells depleted of UPF1 show defects in the release of mRNAs from transcription sites and mRNA export from the nucleus.
Data availability
ChIp-Seq and RNA -Seq data have been deposited in GEO under accession code GSE116808, GSE116806 and GSE116807.
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The RNA helicase UPF1 associates with mRNAs cotranscriptionallyNCBI Gene Expression Omnibus, GSE116808.
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The RNA helicase UPF1 associates with mRNAs cotranscriptionallyNCBI Gene Expression Omnibus, GSE116806.
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The RNA helicase UPF1 associates with mRNAs cotranscriptionallyNCBI Gene Expression Omnibus, GSE116807.
Article and author information
Author details
Funding
Leverhulme Trust (RPG-2014-291)
- Saverio Brogna
Wellcome (9340/Z/09/Z)
- Saverio Brogna
Biotechnology and Biological Sciences Research Council (BB/M022757/1)
- Saverio Brogna
Biotechnology and Biological Sciences Research Council (BB/M017982/1)
- Daniel Hebenstreit
Biotechnology and Biological Sciences Research Council (BB/L006340/1)
- Daniel Hebenstreit
The author declare that funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Robert H Singer, Albert Einstein College of Medicine, United States
Version history
- Received: August 26, 2018
- Accepted: March 22, 2019
- Accepted Manuscript published: March 25, 2019 (version 1)
- Version of Record published: April 3, 2019 (version 2)
Copyright
© 2019, Singh 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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