The ribonuclease FttA (also known as aCPSF and aCPSF1) mediates factor-dependent transcription termination in archaea^1,2,3. 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.

核糖核酸酶 FttA（也称为 aCPSF 和 aCPSF1）介导古细菌中的因子依赖性转录终止^1,2,3。在这里，我们报道了由 FttA、Spt4、Spt5 和转录延伸复合物 （TEC） 组成的 Thermococcus kodakarensis 转录预终止复合物的结构。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 RNA 能够通过 FttA 进行核酸内切切割，然后通过 FttA 对 RNA 进行 5'→3' 核酸外切切割，并伴随 FttA 在 RNA 上进行 5'→3' 易位， 对 TEC 施加机械力并触发端接。该结构进一步揭示了 Spt5 桥接 FttA 和 TEC，解释了 Spt5 如何刺激 FttA 依赖性终止。结果揭示了细菌和古细菌因子依赖性终止之间的功能类比，古细菌和真核生物因子依赖性终止之间的功能同源性，以及细菌、古细菌和真核生物中因子依赖性终止的基本机制相似性。