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| Subject Categories: RNA |
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| The EMBO Journal
(2007) 26, 1591–1601, doi:10.1038/sj.emboj.7601588 Published online 22 February 2007 |
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| A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay |
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| Isabelle Behm-Ansmant1, David Gatfield2, 3, Jan Rehwinkel2, Valérie Hilgers2 and Elisa Izaurralde1, 2 |
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1 Max-Planck-Institute for Developmental Biology, Tübingen, Germany 2 EMBL, Heidelberg, Germany To whom correspondence should be addressed Elisa Izaurralde, Max-Planck-Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany. Tel.: +49 7071 601 1350; Fax: +49 7071 601 1353; E-mail: elisa.izaurralde@tuebingen.mpg.de 3 Present address: University of Geneva, Quai Ernest-Ansermet, 1211-Geneva, Switzerland Received 3 October 2006; Accepted 12 January 2007; Published online 22 February 2007. |
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| Abstract |
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| The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs with premature translation termination codons (PTCs). The mechanisms by which PTCs and natural stop codons are discriminated remain unclear. We show that the position of stops relative to the poly(A) tail (and thus of PABPC1) is a critical determinant for PTC definition in Drosophila melanogaster. Indeed, tethering of PABPC1 downstream of a PTC abolishes NMD. Conversely, natural stops trigger NMD when the length of the 3' UTR is increased. However, many endogenous transcripts with exceptionally long 3' UTRs escape NMD, suggesting that the increase in 3' UTR length has co-evolved with the acquisition of features that suppress NMD. We provide evidence for the existence of 3' UTRs conferring immunity to NMD. We also show that PABPC1 binding is sufficient for PTC recognition, regardless of cleavage or polyadenylation. The role of PABPC1 in NMD must go beyond that of providing positional information for PTC definition, because its depletion suppresses NMD under conditions in which translation efficiency is not affected. These findings reveal a conserved role for PABPC1 in mRNA surveillance. |
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| Keywords: mRNA decay, NMD, PABPC1, UPFs |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSMaking structural sense of nonsense-mediated decay Nature Structural & Molecular Biology News and Views (01 Apr 2004) No mercy for messages that mess with the ribosome Nature Structural & Molecular Biology News and Views (01 Apr 2006) RESEARCHA conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay The EMBO Journal Article Nonsense-mediated mRNA decay in Drosophila:at the intersection of the yeast and mammalian pathways The EMBO Journal Article (01 Aug 2003) |
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