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

被引:57
作者
Luke, Brian [1 ]
Azzalin, Claus M. [1 ]
Hug, Nele [1 ]
Deplazes, Anna [2 ]
Peter, Matthias [2 ]
Lingner, Joachim [1 ]
机构
[1] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res, NCCR Program Frontier Genet, CH-1066 Epalinges, Switzerland
[2] ETH Honggerberg, Swiss Fed Inst Technol Zurich, Inst Biochem, HPM, CH-8093 Zurich, Switzerland
关键词
D O I
10.1093/nar/gkm912
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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收藏
页码:7688 / 7697
页数:10
相关论文
共 51 条
[1]   SMG-5, required for C-elegans nonsense-mediated mRNA decay, associates with SMG-2 and protein phosphatase 2A [J].
Anders, KR ;
Grimson, A ;
Anderson, P .
EMBO JOURNAL, 2003, 22 (03) :641-650
[2]   RNA granules [J].
Anderson, P ;
Kedersha, N .
JOURNAL OF CELL BIOLOGY, 2006, 172 (06) :803-808
[3]  
Ausubel F.M., 1991, CURRENT PROTOCOLS MO
[4]  
AZZAALIN CM, 2007, SCIENCE
[5]   The human RNA surveillance factor UPF1 is required for S phase progression and genome stability [J].
Azzalin, CM ;
Lingner, J .
CURRENT BIOLOGY, 2006, 16 (04) :433-439
[6]   A mouse cytoplasmic exoribonuclease (mXRN1p) with preference for G4 tetraplex substrates [J].
Bashkirov, VI ;
Scherthan, H ;
Solinger, JA ;
Buerstedde, JM ;
Heyer, WD .
JOURNAL OF CELL BIOLOGY, 1997, 136 (04) :761-773
[7]   Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay [J].
Bhattacharya, A ;
Czaplinski, K ;
Trifillis, P ;
He, F ;
Jacobson, A ;
Peltz, SW .
RNA, 2000, 6 (09) :1226-1235
[8]   Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies [J].
Brengues, M ;
Teixeira, D ;
Parker, R .
SCIENCE, 2005, 310 (5747) :486-489
[9]   Identification of delta helicase as the bovine homolog of HUPF1: demonstration of an interaction with the third subunit of DNA polymerase delta [J].
Carastro, LM ;
Tan, CK ;
Selg, M ;
Jack, HM ;
So, AG ;
Downey, KM .
NUCLEIC ACIDS RESEARCH, 2002, 30 (10) :2232-2243
[10]   Characterization of human Smg5/7a:: A protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1 [J].
Chiu, SY ;
Serin, G ;
Ohara, O ;
Maquat, LE .
RNA, 2003, 9 (01) :77-87