Department of Physics and Astronomy, and Institute of Applied Physics, Seoul National University, Seoul 08826, Republic of Korea.
Department of Biological Sciences, and KAIST Stem Cell Center, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Biochem Soc Trans. 2024 Apr 24;52(2):887-897. doi: 10.1042/BST20231229.
Transcription termination has evolved to proceed through diverse mechanisms. For several classes of terminators, multiple models have been debatably proposed. Recent single-molecule studies on bacterial terminators have resolved several long-standing controversies. First, termination mode or outcome is twofold rather than single. RNA is released alone before DNA or together with DNA from RNA polymerase (RNAP), i.e. with RNA release for termination, RNAP retains on or dissociates off DNA, respectively. The concomitant release, described in textbooks, results in one-step decomposition of transcription complexes, and this 'decomposing termination' prevails at ρ factor-dependent terminators. Contrastingly, the sequential release was recently discovered abundantly from RNA hairpin-dependent intrinsic terminations. RNA-only release allows RNAP to diffuse on DNA in both directions and recycle for reinitiation. This 'recycling termination' enables one-dimensional reinitiation, which would be more expeditious than three-dimensional reinitiation by RNAP dissociated at decomposing termination. Second, while both recycling and decomposing terminations occur at a hairpin-dependent terminator, four termination mechanisms compatibly operate at a ρ-dependent terminator with ρ in alternative modes and even intrinsically without ρ. RNA-bound catch-up ρ mediates recycling termination first and decomposing termination later, while RNAP-prebound stand-by ρ invokes only decomposing termination slowly. Without ρ, decomposing termination occurs slightly and sluggishly. These four mechanisms operate on distinct timescales, providing orderly fail-safes. The stand-by mechanism is benefited by terminational pause prolongation and modulated by accompanying riboswitches more greatly than the catch-up mechanisms. Conclusively, any mechanism alone is insufficient to perfect termination, and multiple mechanisms operate compatibly to achieve maximum possible efficiency under separate controls.
转录终止已经进化出多种不同的机制。对于几类终止子，已经提出了一些有争议的模型。最近对细菌终止子的单分子研究解决了几个长期存在的争议。首先，终止模式或结果是双重的，而不是单一的。RNA 是在 DNA 之前还是与 RNA 聚合酶（RNAP）一起从 RNA 中释放，即终止时 RNA 释放，RNAP 保留在 DNA 上或从 DNA 上解离，分别是单独的或一起的。在教科书中描述的伴随释放导致转录复合物的一步分解，这种“分解终止”在 ρ 因子依赖的终止子中占主导地位。相比之下，最近从 RNA 发夹依赖的内在终止子中大量发现了顺序释放。仅 RNA 释放允许 RNAP 在 DNA 上双向扩散并回收以重新起始。这种“回收终止”允许一维重新起始，这比通过在分解终止中解离的 RNAP 进行三维重新起始更快。其次，虽然在发夹依赖的终止子上都发生了回收和分解终止，但在 ρ 依赖的终止子上，四种终止机制可以在 ρ 以不同的模式，甚至在没有 ρ 的情况下兼容地发挥作用。与 RNA 结合的追赶 ρ 首先介导回收终止，然后是分解终止，而 RNAP 预先结合的备用 ρ 缓慢地仅引发分解终止。没有 ρ，分解终止发生得稍慢。这四种机制在不同的时间尺度上运作，提供有序的故障安全措施。备用机制受益于终止暂停的延长，并受到伴随的核糖开关的更大调节，比追赶机制更受调节。总之，任何单一机制都不足以完美终止，多种机制在单独的控制下兼容地运作，以实现最大可能的效率。
