SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export

Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evalu
Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evaluate members of the SR protein family (SRSF1-7) for their potential to act as NXF1 adaptors that couple pre-mRNA processing to mRNA export. Consistent with this proposal, >1000 endogenous mRNAs required individual SR proteins for nuclear export in vivo. To address the mechanism, transcriptome-wide RNA-binding profiles of NXF1 and SRSF1-7 were determined in parallel by individual-nucleotide-resolution UV cross-linking and immunoprecipitation (iCLIP). Quantitative comparisons of RNA-binding sites showed that NXF1 and SR proteins bind mRNA targets at adjacent sites, indicative of cobinding. SRSF3 emerged as the most potent NXF1 adaptor, conferring sequence specificity to RNA binding by NXF1 in last exons. Interestingly, SRSF3 and SRSF7 were shown to bind different sites in last exons and regulate 3' untranslated region length in an opposing manner. Both SRSF3 and SRSF7 promoted NXF1 recruitment to mRNA. Thus, SRSF3 and SRSF7 couple alternative splicing and polyadenylation to NXF1-mediated mRNA export, thereby controlling the cytoplasmic abundance of transcripts with alternative 3' ends. 
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Author:Michaela Müller-McNicoll, Valentina Botti, Antonio M. de Jesus Domingues, Holger Brandl, Oliver D. Schwich, Christina Michaela Steiner, Tomaz Curk, Ina Poser, Kathi Zarnack, Karla M. Neugebauer
URN:urn:nbn:de:hebis:30:3-412893
DOI:http://dx.doi.org/10.1101/gad.276477.115
ISSN:0890-9369
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=26944680
Parent Title (English):Genes & Development
Publisher:Cold Spring Harbor Laboratory Press
Document Type:Article
Language:English
Year of Completion:2016
Year of first Publication:2016
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/07/18
Tag:NXF1; SR protein; SRSF3; SRSF7; alternative 3′ end processing; iCLIP; mRNA export
Volume:30
Issue:5
First Page:553
Last Page:556
Note:
© 2016 Müller-McNicoll et al. This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
HeBIS PPN:427780497
Institutes:Biowissenschaften
Medizin
Dewey Decimal Classification:570 Biowissenschaften; Biologie
610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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