Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of mammalian splicing factors are often focused on small nuclear ribonucleoproteins or regulatory RNA-binding proteins, such as hnRNP (heterogeneous nuclear ribonucleoprotein) and SR proteins (serine/arginine-rich proteins); however, much less is known about the contribution of DExD/H-box proteins or RNA helicases in mammalian pre-mRNA splicing. The human DEAH-box protein DHX16 [also known as DBP2 (DEAD-box protein 2)], is homologous with Caenorhabditis elegans Mog-4, Schizosaccharomyces pombe Prp8 and Saccharomyces cerevisiae Prp2. In the present study, we show that DHX16 is required for pre-mRNA splicing after the formation of a pre-catalytic spliceosome. We found that anti-DHX16 antiserum inhibited the splicing reaction in vitro and the antibody immunoprecipitated pre-mRNA, splicing intermediates and spliceosomal small nuclear RNAs. Cells that expressed DHX16 that had a mutation in the helicase domain accumulated unspliced intron-containing minigene transcripts. Nuclear extracts isolated from the dominant-negative DHX16-G724N-expressing cells formed splicing complex B, but were impaired in splicing. Adding extracts containing DHX16-G724N or DHX16-S552L mutant proteins to HeLa cell nuclear extracts resulted in reduced splicing, indicating that the mutant protein directly inhibited splicing in vitro. Therefore our results show that DHX16 is needed for human pre-mRNA splicing at a step analogous to that mediated by the S. cerevisiae spliceosomal ATPase Prp2.
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PMID:Contribution of DEAH-box protein DHX16 in human pre-mRNA splicing. 2042 32

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.
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PMID:The DEAD-box RNA helicase Dbp2 connects RNA quality control with repression of aberrant transcription. 2267 25

Cellular homeostasis requires a fine balance between energy uptake, utilization, and growth. Dbp2 is a member of the DEAD-box protein family in Saccharomyces cerevisiae with characterized ATPase and helicase activity in vitro. DEAD-box RNA helicases are a class of enzymes that utilize ATP hydrolysis to remodel RNA and/or RNA-protein (RNP) composition. Dbp2 has been proposed to utilize its helicase activity in vivo to promote RNA-protein complex assembly of both messenger (m)RNAs and long noncoding (lnc)RNAs. Previous work from our laboratory demonstrated that loss of DBP2 enhances the lncRNA-dependent transcriptional induction of the GAL genes by abolishing glucose-dependent repression. Herein, we report that either a carbon source switch or glucose deprivation results in rapid export of Dbp2 to the cytoplasm. Genome-wide RNA sequencing identified a new class of antisense hexose transporter transcripts that are specifically upregulated upon loss of DBP2. Further investigation revealed that both sense and antisense hexose transporter (HXT) transcripts are aberrantly expressed in DBP2-deficient cells and that this expression pathway can be partially mimicked in wild-type cells by glucose depletion. We also find that Dbp2 promotes ribosome biogenesis and represses alternative ATP-producing pathways, as loss of DBP2 alters the transcript levels of ribosome biosynthesis (snoRNAs and associated proteins) and respiration gene products. This suggests that Dbp2 is a key integrator of nutritional status and gene expression programs required for energy homeostasis.
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PMID:Regulation of glucose-dependent gene expression by the RNA helicase Dbp2 in Saccharomyces cerevisiae. 2516 81