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Molecular and Cellular Biology, November 2001, p. 7366-7379, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7366-7379.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Absence of Dbp2p Alters Both Nonsense-Mediated mRNA Decay and rRNA Processing

Andrew T. Bond,dagger David A. Mangus, Feng He, and Allan Jacobson*

Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0122

Received 23 May 2001/Returned for modification 3 July 2001/Accepted 7 August 2001

Dbp2p, a member of the large family of DEAD-box proteins and a yeast homolog of human p68, was shown to interact with Upf1p, an essential component of the nonsense-mediated mRNA decay pathway. Dbp2p:Upf1p interaction occurs within a large conserved region in the middle of Upf1p that is largely distinct from its Nmd2p and Sup35/45p interaction domains. Deletion of DBP2, or point mutations within its highly conserved DEAD-box motifs, increased the abundance of nonsense-containing transcripts, leading us to conclude that Dbp2p also functions in the nonsense-mediated mRNA decay pathway. Dbp2p, like Upf1p, acts before or at decapping, is predominantly cytoplasmic, and associates with polyribosomes. Interestingly, Dbp2p also plays an important role in rRNA processing. In dbp2Delta cells, polyribosome profiles are deficient in free 60S subunits and the mature 25S rRNA is greatly reduced. The ribosome biogenesis phenotype, but not the mRNA decay function, of dbp2Delta cells can be complemented by the human p68 gene. We propose a unifying model in which Dbp2p affects both nonsense-mediated mRNA decay and rRNA processing by altering rRNA structure, allowing specific processing events in one instance and facilitating dissociation of the translation termination complex in the other.


* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of Massachusetts, Medical School, 55 Lake Ave. North, Worcester, MA 01655-0122. Phone: (508) 856-2442. Fax: (508) 856-5920. E-mail: allan.jacobson{at}umassmed.edu.

dagger Present address: Abbott Bioresearch Center, Worcester, MA 06105.


Molecular and Cellular Biology, November 2001, p. 7366-7379, Vol. 21, No. 21
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.21.7366-7379.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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