Abstract
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.
Highlights
Dbp2 is a member of the DEAD-box family of RNA helicases
DBP2 Is an RNA-dependent ATPase in Vitro—Dbp2 is a member of the DEAD-box family of RNA-dependent ATPases in S. cerevisiae based on the presence of 10 conserved sequence motifs organized into two distinct structural domains (Fig. 1A) [11]
GAL7 Transcripts Are Overabundant in the Absence of DBP2— Given that DBP2-deficient cells display defects associated with active transcription, we asked if DBP2 is required for normal expression levels of endogenous genes (Fig. 3F)
Summary
Dbp is a member of the DEAD-box family of RNA helicases. Results: Dbp is a double-stranded RNA-specific ATPase required for repression of cryptic initiation and downstream RNA quality control. Whereas the precise function of these molecules is still hotly debated, it is clear that regulation is accomplished through the same mechanisms as those utilized for protein-coding mRNAs. lncRNAs are substrates for the nuclear exosome, a multiprotein complex responsible for maturation and degradation of numerous noncoding RNAs and aberrantly processed mRNAs [7]. Ϩ pdbp2-K136N/CEN/LEU2 MATa dbp2::KanMx ura3⌬0 leu2⌬0 his3⌬0 TRP1 met- lys? Dbp has only been linked to ribosome biogenesis and non-sense-mediated decay in S. cerevisiae despite the fact that human p68 functionally complements loss of DBP2 (16 –18) This suggests that a role in transcriptional processes is either not conserved or that Dbp plays an as-ofyet uncharacterized function in budding yeast. This would provide a model RNA modulation during transcription with broad implications to other aspects of RNA biology
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