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Nucleic Acids Research Advance Access originally published online on November 4, 2007
Nucleic Acids Research 2007 35(22):7688-7697; doi:10.1093/nar/gkm912
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Nucleic Acids Research, 2007, Vol. 35, No. 22 7688-7697
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


RNA

Saccharomyces cerevisiae Ebs1p is a putative ortholog of human Smg7 and promotes nonsense-mediated mRNA decay

Brian Luke1, Claus M. Azzalin1, Nele Hug1, Anna Deplazes2, Matthias Peter2 and Joachim Lingner1,*

1Swiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne (EPFL) and NCCR Program ‘Frontiers in Genetics’, 155, Chemin des Boveresses, CH-1066 Epalinges s/Lausanne and 2Swiss Federal Institute of Technology Zurich (ETH), Institute of Biochemistry, ETH Hoenggerberg HPM G 10.0, CH-8093 Zurich, Switzerland

*To whom correspondence should be addressed. Tel: +41 21 692 5870; Fax: +41 21 652 6933; Email: joachim.lingner{at}isrec.ch

Received March 13, 2007. Revised October 4, 2007. Accepted October 8, 2007.

The Smg proteins Smg5, Smg6 and Smg7 are involved in nonsense-mediated RNA decay (NMD) in metazoans, but no orthologs have been found in the budding yeast Saccharomyces cerevisiae. Sequence alignments reveal that yeast Ebs1p is similar in structure to the human Smg5-7, with highest homology to Smg7. We demonstrate here that Ebs1p is involved in NMD and behaves similarly to human Smg proteins. Indeed, both loss and overexpression of Ebs1p results in stabilization of NMD targets. However, Ebs1-loss in yeast or Smg7-depletion in human cells only partially disrupts NMD and in the latter, Smg7-depletion is partially compensated for by Smg6. Ebs1p physically interacts with the NMD helicase Upf1p and overexpressed Ebs1p leads to recruitment of Upf1p into cytoplasmic P-bodies. Furthermore, Ebs1p localizes to P-bodies upon glucose starvation along with Upf1p. Overall our findings suggest that NMD is more conserved in evolution than previously thought, and that at least one of the Smg5-7 proteins is conserved in budding yeast.


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