Genome-Wide Discovery of DEAD-Box RNA Helicase Targets Reveals RNA Structural Remodeling in Transcription Termination

• Published in: Genetics (Austin) 2019-05, Vol.212 (1), p.153-174
• Main Authors: Lai, Yu-Hsuan, Choudhary, Krishna, Cloutier, Sara C, Xing, Zheng, Aviran, Sharon, Tran, Elizabeth J
• Format: Article
• Language: English
• Subjects: DEAD-box RNA Helicases - metabolism; DNA helicase; DNA Helicases - metabolism; DNA-directed RNA polymerase; Enzymes; Gene expression; Gene Expression Regulation, Fungal; Gene regulation; Genetics; Genomes; Investigations; Metabolism; Nuclear Proteins - metabolism; Nucleoli; Nucleotide sequence; Protein structure; Proteins; Ribonucleic acid; RNA; RNA helicase; RNA Helicases - metabolism; RNA polymerase; RNA polymerase II; RNA Polymerase II - metabolism; RNA, Messenger - metabolism; RNA, Small Nucleolar - metabolism; RNA-Binding Proteins - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Sequence Analysis, RNA; Structural stability; Transcription termination; Transcription Termination, Genetic; Yeast
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.119.302058

RNA helicases are a class of enzymes that unwind RNA duplexes but whose cellular functions are largely enigmatic. Here, we provide evidence that the DEAD-box protein Dbp2 remodels RNA-protein complex (RNP) structure to facilitate efficient termination of transcription in via the Nrd1-Nab3-Sen1 (NNS) complex. First, we find that loss of results in RNA polymerase II accumulation at the 3' ends of small nucleolar RNAs and a subset of mRNAs. In addition, Dbp2 associates with RNA sequence motifs and regions bound by Nrd1 and can promote its recruitment to NNS-targeted regions. Using Structure-seq, we find altered RNA/RNP structures in ∆ cells that correlate with inefficient termination. We also show a positive correlation between the stability of structures in the 3' ends and a requirement for Dbp2 in termination. Taken together, these studies provide a role for RNA remodeling by Dbp2 and further suggests a mechanism whereby RNA structure is exploited for gene regulation.