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- Title
Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3′ UTRs.
- Authors
Zünd, David; Gruber, Andreas R; Zavolan, Mihaela; Mühlemann, Oliver
- Abstract
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.
- Subjects
GENETIC translation; SUBSTITUTION reactions; MESSENGER RNA; RIBOSOMES; TRANSLATION initiation factors (Biochemistry); NON-coding RNA; IMMUNOPRECIPITATION
- Publication
Nature Structural & Molecular Biology, 2013, Vol 20, Issue 8, p936
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2635