The DEAD-box RNA helicase Dbp2 connects RNA quality control with repression of aberrant transcription.
DEAD-box proteins are a class of RNA-dependent ATP hydrolysis enzymes that rearrange RNA and RNA-protein (ribonucleoprotein) complexes. In an effort to characterize the cellular function of individual DEAD-box proteins, our laboratory has uncovered a previously unrecognized link between the DEAD-box protein Dbp2 and the regulation of transcription in Saccharomyces cerevisiae. Here, we report that Dbp2 is a double-stranded RNA-specific ATPase that associates directly with chromatin and is required for transcriptional fidelity. In fact, loss of DBP2 results in multiple gene expression defects, including accumulation of noncoding transcripts, inefficient 3' end formation, and appearance of aberrant transcriptional initiation products. We also show that loss of DBP2 is synthetic lethal with deletion of the nuclear RNA decay factor, RRP6, pointing to a global role for Dbp2 in prevention of aberrant transcriptional products. Taken together, we present a model whereby Dbp2 functions to cotranscriptionally modulate RNA structure, a process that facilitates ribonucleoprotein assembly and clearance of transcripts from genomic loci. These studies suggest that Dbp2 is a missing link in RNA quality control that functions to maintain the fidelity of transcriptional processes.
Department of Biochemistry and Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907-2063, USA.
Sara C
SC
Cloutier
Wai Kit
WK
Ma
Luyen T
LT
Nguyen
Elizabeth J
EJ
Tran
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001483:Base Sequence; D002467:Cell Nucleus / Q000201:enzymology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005095:Exoribonucleases / Q000172:deficiency / Q000235:genetics; D063326:Exosome Multienzyme Ribonuclease Complex; D015966:Gene Expression Regulation, Fungal; D055785:Gene Knockdown Techniques; D005800:Genes, Fungal; D055029:Inverted Repeat Sequences; D005810:Multigene Family; D016366:Open Reading Frames; D011485:Protein Binding; D012323:RNA Processing, Post-Transcriptional; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic
D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C112610:RRP6 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C438898:Dbp2 protein, S cerevisiae; D053487:DEAD-box RNA Helicases