A cooperative PNPase-Hfq-RNA carrier complex facilitates bacterial riboregulation.

A cooperative PNPase-Hfq-RNA carrier complex facilitates bacterial riboregulation.
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DOI:
10.1016/j.molcel.2021.05.032
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发表时间:
2021-07-15
期刊:
影响因子:
16
通讯作者:
Bandyra KJ
Bandyra KJ
中科院分区:
生物学1区
文献类型:
--
作者:
Dendooven T;Sinha D;Roeselová A;Cameron TA;De Lay NR;Luisi BF;Bandyra KJ

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多核苷酸磷酸化酶(PNPase)是一种在进化过程中保守的古老的外切核酸酶,存在于细菌和人类等各种物种中。矛盾的是,大肠杆菌PNPase不仅可以作为一种RNA降解酶,还可以通过一种未知的机制作为小调节RNA(SRNAs)的伴侣,对基因调控具有多效性。我们给出了由PNPase、RNA伴侣Hfq和sRNA形成的三元组装的结构,并表明该络合物在体外提高了sRNA的稳定性。通过比较PNPase在RNA载体和降解模式下的结构,揭示了RNA是如何通过与Hfq以及KH和S1结构域的相互作用而偏离活性部位的。综上所述,这些数据解释了PNPase是如何被重新利用来保护sRNA免受RNase E等细胞核糖核酸酶的影响,并可以帮助RNA提呈以促进对靶基因的调控作用。PNPase的冷冻-EM结构与RNA伴侣Hfq和调控RNA的结构研究Hfq和PNPase对调控RNA识别的结构模型稳定调控RNA和促进其功能的模型保守的外切核酸酶PNPase在许多生物中有助于RNA的周转,但在细菌中,该酶可以被RNA伴侣Hfq和调控RNA重新编程,在RNA介导的基因调控中从降解角色转换为伴侣角色。丹多芬等人。提供对这种功能转换的基础的结构性洞察,以及Hfq和PNPase识别复杂调控RNA的细节。
Polynucleotide phosphorylase (PNPase) is an ancient exoribonuclease conserved in the course of evolution and is found in species as diverse as bacteria and humans. Paradoxically, Escherichia coli PNPase can act not only as an RNA degrading enzyme but also by an unknown mechanism as a chaperone for small regulatory RNAs (sRNAs), with pleiotropic consequences for gene regulation. We present structures of the ternary assembly formed by PNPase, the RNA chaperone Hfq, and sRNA and show that this complex boosts sRNA stability in vitro. Comparison of structures for PNPase in RNA carrier and degradation modes reveals how the RNA is rerouted away from the active site through interactions with Hfq and the KH and S1 domains. Together, these data explain how PNPase is repurposed to protect sRNAs from cellular ribonucleases such as RNase E and could aid RNA presentation to facilitate regulatory actions on target genes. Cryo-EM structures of PNPase in complex with the RNA chaperone Hfq and regulatory RNA Structural insights into regulatory RNA recognition by Hfq and PNPase Model for stabilization of regulatory RNAs and facilitation of their functions The conserved exoribonuclease PNPase contributes to RNA turnover in many organisms, but in bacteria the enzyme can be re-programmed by the RNA chaperone Hfq and regulatory RNA to switch from degradative to chaperoning roles in RNA-mediated gene regulation. Dendooven et al. provide structural insight into the basis for this functional switch and details of the recognition of complex regulatory RNAs by Hfq and PNPase.
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