Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3' UTRs

Zünd, David and Gruber, Andreas R. and Zavolan, Mihaela and Mühlemann, Oliver. (2013) Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3' UTRs. Nature structural & molecular biology, Vol. 20, H. 8 , S. 936–943.

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Official URL: http://edoc.unibas.ch/dok/A6165044

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Recruitment of the UPF1 nonsense-mediated mRNA decay (NMD) factor to target mRNAs was initially proposed to occur through interaction with release factors at terminating ribosomes. However, recently emerging evidence points toward translation-independent interaction with the 3' untranslated region (UTR) of mRNAs. We mapped transcriptome-wide UPF1-binding sites by individual-nucleotide-resolution UV cross-linking and immunoprecipitation in human cells and found that UPF1 preferentially associated with 3' UTRs in translationally active cells but underwent significant redistribution toward coding regions (CDS) upon translation inhibition, thus indicating that UPF1 binds RNA before translation and gets displaced from the CDS by translating ribosomes. Corroborated by RNA immunoprecipitation and by UPF1 cross-linking to long noncoding RNAs, our evidence for translation-independent UPF1-RNA interaction suggests that the triggering of NMD occurs after UPF1 binding to mRNA, presumably through activation of RNA-bound UPF1 by aberrant translation termination.
Faculties and Departments:05 Faculty of Science
05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela and Gruber, Andreas R.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publ. Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Mar 2015 07:44
Deposited On:13 Sep 2013 07:57

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