美国罗格斯大学Richard H. Ebright团队近期取得重要工作进展，他们研究提出，古菌FttA依赖性转录终止的结构基础。相关研究工作2024年9月25日在线发表于《自然》杂志上。

据介绍，核糖核酸酶FttA（也称为aCPSF和aCPSF1）介导古菌中因子依赖性转录终止。

研究人员报告了由FttA、Spt4、Spt5和转录延长复合物（TEC）组成的柯达热球菌转录终止前复合物的结构。该结构表明，FttA与TEC相互作用的方式使RNA能够直接从TEC RNA出口通道进入FttA催化中心，并使FttA能够对RNA进行核酸内切切割，随后是FttA对RNA的5′→3′核酸内切分裂，并伴随着FttA在RNA上的5′～3′易位，从而对TEC施加机械力并触发终止。该结构进一步揭示了Spt5桥接FttA和TEC，解释了Spt5如何刺激FttA依赖的终止。

总之，这一研究揭示了细菌和古菌因子依赖性终止之间的功能相似性，古菌和真核生物因子依赖性终结之间的功能同源性，以及细菌、古菌和真实生物因子依赖终止的基本机制相似性。

附：英文原文

Title: Structural basis of archaeal FttA-dependent transcription termination

Author: You, Linlin, Wang, Chengyuan, Molodtsov, Vadim, Kuznedelov, Konstantin, Miao, Xinyi, Wenck, Breanna R., Ulisse, Paul, Sanders, Travis J., Marshall, Craig J., Firlar, Emre, Kaelber, Jason T., Santangelo, Thomas J., Ebright, Richard H.

Issue&Volume: 2024-09-25

Abstract: The ribonuclease FttA (also known as aCPSF and aCPSF1) mediates factor-dependent transcription termination in archaea1,2,3. Here we report the structure of a Thermococcus kodakarensis transcription pre-termination complex comprising FttA, Spt4, Spt5 and a transcription elongation complex (TEC). The structure shows that FttA interacts with the TEC in a manner that enables RNA to proceed directly from the TEC RNA-exit channel to the FttA catalytic centre and that enables endonucleolytic cleavage of RNA by FttA, followed by 5′→3′ exonucleolytic cleavage of RNA by FttA and concomitant 5′→3′ translocation of FttA on RNA, to apply mechanical force to the TEC and trigger termination. The structure further reveals that Spt5 bridges FttA and the TEC, explaining how Spt5 stimulates FttA-dependent termination. The results reveal functional analogy between bacterial and archaeal factor-dependent termination, functional homology between archaeal and eukaryotic factor-dependent termination, and fundamental mechanistic similarities in factor-dependent termination in bacteria, archaea, and eukaryotes.

DOI: 10.1038/s41586-024-07979-9

Source: https://www.nature.com/articles/s41586-024-07979-9