Absence of Dbp2p alters both nonsense-mediated mRNA decay and rRNA processing
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Blotting, Northern; Canavanine; Cell Nucleus; Conserved Sequence; Cycloheximide; DEAD-box RNA Helicases; Dose-Response Relationship, Drug; Gene Deletion; Models, Biological; Mutation; Oligonucleotides; Paromomycin; Phenotype; Plasmids; Point Mutation; Protein Binding; Protein Biosynthesis; Protein Kinases; Protein Structure, Tertiary; Protein Synthesis Inhibitors; RNA Helicases; RNA, Messenger; RNA, Ribosomal; Ribosomes; Saccharomyces cerevisiae Proteins; Subcellular Fractions; Time Factors; Trans-Activators; Two-Hybrid System Techniques
Life Sciences | Medicine and Health Sciences
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.
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Citation: Mol Cell Biol. 2001 Nov;21(21):7366-79. Link to article on publisher's site
Bond, Andrew T.; Mangus, David A.; He, Feng; and Jacobson, Allan, "Absence of Dbp2p alters both nonsense-mediated mRNA decay and rRNA processing" (2001). GSBS Student Publications. Paper 107.