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Molecular and Cellular Biology, September 1999, p. 5943-5951, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

SMG-2 Is a Phosphorylated Protein Required for mRNA Surveillance in Caenorhabditis elegans and Related to Upf1p of Yeast

Michelle F. Page,1 Brian Carr,1,dagger Kirk R. Anders,2,Dagger Andrew Grimson,2 and Philip Anderson1,2,*

Department of Genetics1 and Program in Cell and Molecular Biology,2 University of Wisconsin, Madison, Wisconsin 53706

Received 5 October 1998/Returned for modification 18 November 1998/Accepted 25 May 1999

mRNAs that contain premature stop codons are selectively degraded in all eukaryotes tested, a phenomenon termed "nonsense-mediated mRNA decay" (NMD) or "mRNA surveillance." NMD may function to eliminate aberrant mRNAs so that they are not translated, because such mRNAs might encode deleterious polypeptide fragments. In both yeasts and nematodes, NMD is a nonessential system. Mutations affecting three yeast UPF genes or seven nematode smg genes eliminate NMD. We report here the molecular analysis of smg-2 of Caenorhabditis elegans. smg-2 is homologous to UPF1 of yeast and to RENT1 (also called HUPF1), a human gene likely involved in NMD. The striking conservation of SMG-2, Upf1p, and RENT1/HUPF1 in both sequence and function suggests that NMD is an ancient system, predating the divergence of most eukaryotes. Despite similarities in the sequences of SMG-2 and Upf1p, expression of Upf1p in C. elegans does not rescue smg-2 mutants. We have prepared anti-SMG-2 polyclonal antibodies and identified SMG-2 on Western blots. SMG-2 is phosphorylated, and mutations of the six other smg genes influence the state of SMG-2 phosphorylation. In smg-1, smg-3, and smg-4 mutants, phosphorylation of SMG-2 was not detected. In smg-5, smg-6, and smg-7 mutants, a phosphorylated isoform of SMG-2 accumulated to abnormally high levels. In smg-2(r866) and smg-2(r895) mutants, which harbor single amino acid substitutions of the SMG-2 nucleotide binding site, phosphorylated SMG-2 accumulated to abnormally high levels, similar to those observed in smg-5, smg-6, and smg-7 mutants. We discuss these results with regard to the in vivo functions of SMG-2 and NMD.

* Corresponding author. Mailing address: Department of Genetics, University of Wisconsin, 445 Henry Mall, Madison, WI 53706. Phone: (608) 263-8429. Fax: (608) 262-2976. E-mail: andersn{at}facstaff.wisc.edu.

dagger Present address: Maxygen, Inc., Redwood City, CA 94063.

Dagger Present address: Department of Genetics, Stanford University Medical Center, Stanford, CA 94305.

Molecular and Cellular Biology, September 1999, p. 5943-5951, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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