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Molecular and Cellular Biology, November 1999, p. 7568-7576, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mutations in VPS16 and MRT1 Stabilize mRNAs by Activating an Inhibitor of the Decapping Enzyme

Shuang Zhang,1,2 Carol J. Williams,1 Kevin Hagan,1 and Stuart W. Peltz1,2,3,*

Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey,1 and Graduate Program in Molecular Biosciences,2 UMDNJ-Robert Wood Johnson/Rutgers Universities, and Cancer Institute of New Jersey,3 Piscataway, New Jersey 08854

Received 4 May 1999/Returned for modification 11 June 1999/Accepted 19 July 1999

Decapping is a rate-limiting step in the decay of many yeast mRNAs; the activity of the decapping enzyme therefore plays a significant role in determining RNA stability. Using an in vitro decapping assay, we have identified a factor, Vps16p, that regulates the activity of the yeast decapping enzyme, Dcp1p. Mutations in the VPS16 gene result in a reduction of decapping activity in vitro and in the stabilization of both wild-type and nonsense-codon-containing mRNAs in vivo. The mrt1-3 allele, previously shown to affect the turnover of wild-type mRNAs, results in a similar in vitro phenotype. Extracts from both vps16 and mrt1 mutant strains inhibit the activity of purified Flag-Dcp1p. We have identified a 70-kDa protein which copurifies with Flag-Dcp1p as the abundant Hsp70 family member Ssa1p/2p. Intriguingly, the interaction with Ssa1p/2p is enhanced in strains with mutations in vps16 or mrt1. We propose that Hsp70s may be involved in the regulation of mRNA decapping.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, UMDNJ-Robert Wood Johnson/Rutgers, 675 Hoes Ln., Piscataway, NJ 08854. Phone: (732) 235-4790. Fax: (732) 235-5223. E-mail: Peltz{at}UMDNJ.EDU.

Molecular and Cellular Biology, November 1999, p. 7568-7576, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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