Molecule of the Month
December 2013
Transcriptome-Wide Mapping of UPF1 Binding Sites Reveals Evidence for its Recruitment to mRNA Before Translation

Recruitment of the UPF1 nonsense-mediated mRNA decay (NMD) factor to target mRNAs was initially proposed to occur through interaction with 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 (iCLIP) in human cells and found that UPF1 preferentially associates with 3 UTRs in translationally active cells but underwent significant redistribution toward coding regions (CDS) upon translation inhibition, thus indicating that UPF1 binds mRNA before translation and gets displaced by the translating ribosome.
The CDS, starting with an AUG and ending with a stop codon (UGA), is depicted by a box, which is flanked by the 3 UTR and the 5 UTR, respectively. UPF1 is represented as orange ovals and the ribosome translating the ORF is shown in red.

This work was carried out in the group of Prof. Oliver Mühlemann.

References:

  • D. Zünd, A. R. Gruber, M. Zavolan, O. Mühlemann;
    "Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3 UTRs"
    Nat. Struct. Mol. Biol., 20, 936-943, (2013); doi:10.1038/nsmb.2635.
  • J. Robert Hogg, Stephen P. Goff;
    "Upf1 Senses 3'UTR Length to Potentiate mRNA Decay"
    Cell, 143, 379-389, (2010); doi:10.1016/j.cell.2010.10.005.