Absence of Dbp2p alters both nonsense-mediated mRNA decay and rRNA processing

Dbp2p, a member of the large family of DEAD-box proteins and a yeast homolo g of human p68, was shown to interact with Upf1p, an essential component of the nonsense-mediated mRNA decay pathway. Dbp2p:Upf1p interaction occurs w ithin a large conserved region in the middle of Upf1p that is largely disti nct 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 D bp2p also functions in the nonsense-mediated mRNA decay pathway. Dbp2p, lik e Upf1p, acts before or at decapping, is predominantly cytoplasmic, and ass ociates with polyribosomes. Interestingly, Dbp2p also plays an important ro le in rRNA processing. In dbp2 Delta cells, polyribosome profiles are defic ient in free 60S subunits and the mature 25S rRNA is greatly reduced. The r ibosome biogenesis phenotype, but not the mRNA decay function, of dbp2 Delt a cells can be complemented by the human p68 gene. We propose a unifying mo del in which Dbp2p affects both nonsense-mediated mRNA decay and rRNA proce ssing by altering rRNA structure, allowing specific processing events in on e instance and facilitating dissociation of the translation termination com plex in the other.