The DEAD-box RNA Helicase Dbp2 Connects RNA Quality Control with Repression of Aberrant Transcription

• Published in: The Journal of biological chemistry 2012-07, Vol.287 (31), p.26155-26166
• Main Authors: Cloutier, Sara C., Ma, Wai Kit, Nguyen, Luyen T., Tran, Elizabeth J.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Adenosine Triphosphatases - physiology; Autoimmunity; Base Sequence; Cell Nucleus - enzymology; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; DEAD-box RNA Helicases - physiology; Effector T Cells; Exoribonucleases - deficiency; Exoribonucleases - genetics; Exosome Multienzyme Ribonuclease Complex; Gene Expression Regulation, Fungal; Gene Knockdown Techniques; Gene Regulation; Genes, Fungal; Histone; Histone Deacetylase; Inflammation; Inverted Repeat Sequences; Kidney; Lymphocyte; Multigene Family; Open Reading Frames; Peroxisome Proliferator-activated Receptor; Protein Binding; RNA Processing, Post-Transcriptional; RNA, Fungal - genetics; RNA, Fungal - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; RNA-Binding Proteins - physiology; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Saccharomyces cerevisiae Proteins - physiology; Transcription, Genetic
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.383075

Background: Dbp2 is a member of the DEAD-box family of RNA helicases. Results: Dbp2 is a double-stranded RNA-specific ATPase required for repression of cryptic initiation and downstream RNA quality control. Conclusion: Dbp2 functions in transcriptional fidelity as a cotranscriptional RNA chaperone. Significance: Elucidation of key RNA enzymes is central to defining the mechanisms for eukaryotic gene regulation. 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.