英国纽卡斯尔大学Nikolay Zenkin课题组发现，翻译选择性地破坏无功能的转录复合物。相关论文于2024年2月7日在线发表于国际学术期刊《自然》。

研究人员发现，细菌中与转录偶联的翻译会主动将停滞的转录延伸复合体（EC）从受损的DNA模板中移除。与此相反，停顿但在其他方面具有延伸能力的EC不会被核糖体移除。相反，核糖体会帮助它们重新进入过程性延伸。研究人员还发现，核糖体在接近暂停而非停滞的EC时速度会减慢。这些研究结果表明，偶联核糖体在功能和动力学上可区分暂停的EC和停滞的EC，确保只选择性地破坏后者。这种功能性区分是由RNA聚合酶的催化结构域（触发环）控制的。

该研究表明，转录偶联DNA修复螺旋酶UvrD被认为会导致停滞的EC反向追踪，但它不会干扰核糖体介导的脱位。相比之下，转录偶联DNA修复易位酶Mfd4与翻译起协同作用，能使未被核糖体破坏的停滞EC移位。研究人员还发现，偶联的核糖体能有效地破坏可能与复制发生冲突的错误结合的EC5。研究人员认为，与翻译偶联是一种古老的机制，也是清除基因组中无功能EC的主要机制之一。

据悉，转录延伸在DNA模板的病变处停滞。要修复DNA病变，必须将停滞的EC从受损部位移除。

附：英文原文

Title: Translation selectively destroys non-functional transcription complexes

Author: Woodgate, Jason, Mosaei, Hamed, Brazda, Pavel, Stevenson-Jones, Flint, Zenkin, Nikolay

Issue&Volume: 2024-02-07

Abstract: Transcription elongation stalls at lesions in the DNA template1. For the DNA lesion to be repaired, the stalled transcription elongation complex (EC) has to be removed from the damaged site2. Here we show that translation, which is coupled to transcription in bacteria, actively dislodges stalled ECs from the damaged DNA template. By contrast, paused, but otherwise elongation-competent, ECs are not dislodged by the ribosome. Instead, they are helped back into processive elongation. We also show that the ribosome slows down when approaching paused, but not stalled, ECs. Our results indicate that coupled ribosomes functionally and kinetically discriminate between paused ECs and stalled ECs, ensuring the selective destruction of only the latter. This functional discrimination is controlled by the RNA polymerase’s catalytic domain, the Trigger Loop. We show that the transcription-coupled DNA repair helicase UvrD, proposed to cause backtracking of stalled ECs3, does not interfere with ribosome-mediated dislodging. By contrast, the transcription-coupled DNA repair translocase Mfd4 acts synergistically with translation, and dislodges stalled ECs that were not destroyed by the ribosome. We also show that a coupled ribosome efficiently destroys misincorporated ECs that can cause conflicts with replication5. We propose that coupling to translation is an ancient and one of the main mechanisms of clearing non-functional ECs from the genome.

DOI: 10.1038/s41586-023-07014-3

Source: https://www.nature.com/articles/s41586-023-07014-3