Molecular identification of smg-4, required for mRNA surveillance in C. elegans

被引:24
作者
Aronoff, R
Baran, R
Hodgkin, J
机构
[1] Max Planck Inst Med Res, D-69120 Heidelberg, Germany
[2] Univ Calif Santa Cruz, Sinsheimer Labs, Santa Cruz, CA 95064 USA
[3] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
关键词
nonsense mRNA; mutant rescue; alternative splice;
D O I
10.1016/S0378-1119(01)00414-0
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Premature termination codons trigger a process in eukaryotes known as nonsense mediated decay or mRNA surveillance, resulting in the rapid decay of the aberrant transcript. Studies in C. elegans have shown this system is mediated by seven smg genes and can prevent the accumulation of toxic, truncated peptides. Here we report the cloning of smg-4 by physical mapping and functional rescue assays. The minimal rescuing activity is found within a genomic operon, encoding a novel protein. The final exon of the gene is alternatively spliced for expression of two different isoforms. Although no known genes were found to exhibit significant homology to smg-4, a novel conserved domain has been identified by alignment with sequences defined by expressed sequence tags (ESTs) from a variety of organisms. Furthermore, we describe a homolog from C, briggsae, which will rescue C. elegans smg-4 mutants. The C. elegans gene has been fused to green fluorescent protein (GFP). This SMG4:GFP fusion exhibits nuclear accumulation and diffuse cytoplasmic staining, and further localizes to what appear to be perinuclear and cytoplasmic punctate structures. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:153 / 164
页数:12
相关论文
共 36 条
[11]   The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs [J].
Czaplinski, K ;
Ruiz-Echevarria, MJ ;
Paushkin, SV ;
Han, X ;
Weng, YM ;
Perlick, HA ;
Dietz, HC ;
Ter-Avanesyan, MD ;
Peltz, SW .
GENES & DEVELOPMENT, 1998, 12 (11) :1665-1677
[12]  
Favello A, 1995, METHOD CELL BIOL, V48, P551
[13]   Upf1p, Nmd2p, and Upf3p are interacting components of the yeast nonsense-mediated mRNA decay pathway [J].
He, F ;
Brown, AH ;
Jacobson, A .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (03) :1580-1594
[14]   A perfect message: RNA surveillance and nonsense-mediated decay [J].
Hentze, MW ;
Kulozik, AE .
CELL, 1999, 96 (03) :307-310
[15]   A SEQUENCE PROPERTY APPROACH TO SEARCHING PROTEIN DATABASES [J].
HOBOHM, U ;
SANDER, C .
JOURNAL OF MOLECULAR BIOLOGY, 1995, 251 (03) :390-399
[16]  
HODGKIN J, 1989, GENETICS, V123, P301
[17]  
KOHARA Y, 1997, EXPRESSION MAP C ELE
[18]   IDENTIFICATION OF AN ADDITIONAL GENE REQUIRED FOR EUKARYOTIC NONSENSE MESSENGER-RNA TURNOVER [J].
LEE, BS ;
CULBERTSON, MR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (22) :10354-10358
[19]   GENE-PRODUCTS THAT PROMOTE MESSENGER-RNA TURNOVER IN SACCHAROMYCES-CEREVISIAE [J].
LEEDS, P ;
WOOD, JM ;
LEE, BS ;
CULBERTSON, MR .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (05) :2165-2177
[20]  
Lelivelt MJ, 1999, MOL CELL BIOL, V19, P6710