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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,
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 dbp2
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 dbp2
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.

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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