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全基因组发现 DEAD-Box RNA 解旋酶靶标揭示了转录终止过程中的 RNA 结构重塑。

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

机构信息

Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907-2063.

Department of Biomedical Engineering and Genome Center, University of California, Davis, California 95616.

出版信息

Genetics. 2019 May;212(1):153-174. doi: 10.1534/genetics.119.302058. Epub 2019 Mar 22.

Abstract

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.

摘要

RNA 解旋酶是一类能够解开 RNA 双链的酶,但它们的细胞功能在很大程度上仍是个谜。在这里,我们提供的证据表明 DEAD 盒蛋白 Dbp2 通过 Nrd1-Nab3-Sen1(NNS)复合物重塑 RNA-蛋白质复合物(RNP)结构,以促进在 中的转录有效终止。首先,我们发现缺失 会导致 RNA 聚合酶 II 在小核仁 RNA 和一部分 mRNA 的 3' 末端积累。此外,Dbp2 与 Nrd1 结合的 RNA 序列基序和区域相关联,并能促进其募集到 NNS 靶向区域。通过结构测序,我们发现 ∆ 细胞中的 RNA/RNP 结构发生改变,与终止效率低下相关。我们还表明,3' 末端结构的稳定性与终止过程中需要 Dbp2 之间存在正相关。总之,这些研究为 Dbp2 通过 RNA 重塑发挥作用提供了证据,并进一步表明了一种利用 RNA 结构进行基因调控的机制。

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