Molecular Microbiology Laboratory, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi U.P.-221005, India.
Department of Microbiology, School of life Sciences, Sikkim University, Gangtok 737102, Sikkim, India.
Infect Genet Evol. 2024 Sep;123:105645. doi: 10.1016/j.meegid.2024.105645. Epub 2024 Jul 26.
Bacterial responses to continuously changing environments are addressed through modulation of gene expression at the level of transcription initiation, RNA processing and/or decay. Ribonucleases (RNases) are hydrolytic or phosphorolytic enzymes involved in a majority of RNA metabolism reactions. RNases play a crucial role in RNA degradation, either independently or in collaboration with various trans-acting regulatory factors. The genus Mycobacterium consists of five subgenera: Mycobacteroides, Mycolicibacterium, Mycobacterium, Mycolicibacter and Mycolicibacillus, which include 63 fully sequenced species (pathogenic/non-pathogenic) to date. These include 13 different RNases, among which 5 are exonucleases (RNase PH, PNPase, RNase D, nano-RNases and RNase AS) and 8 are endonucleases (RNase J, RNase H, RNase P, RNase III, RNase BN, RNase Z, RNase G and RNase E), although RNase J and RNase BN were later identified to have exoribonuclease functions also. Here, we provide a detailed comparative insight into the Escherichia coli and mycobacterial RNases with respect to their types, phylogeny, structure, function, regulation and mechanism of action, with the main emphasis on RNase E. Among these 13 different mycobacterial RNases, 10 are essential for cell survival and have diverse structures hence, they are promising drug targets. RNase E is also an essential endonuclease that is abundant in many bacteria, forms an RNA degradosome complex that controls central RNA processing/degradation and has a conserved 5' sensor domain/DNase-I like region in its RNase domain. The essential mycobacterial RNases especially RNase E provide a potential repertoire of drug targets that can be exploited for inhibitor/modulator screening against many deadly mycobacterial diseases.
细菌通过转录起始、RNA 加工和/或降解水平的基因表达调控来应对不断变化的环境。核糖核酸酶（RNases）是参与大多数 RNA 代谢反应的水解或磷酸解酶。RNases 在 RNA 降解中发挥着至关重要的作用，无论是独立作用还是与各种反式作用调节因子协同作用。分枝杆菌属包括五个亚属：Mycobacteroides、Mycolicibacterium、Mycobacterium、Mycolicibacter 和 Mycolicibacillus，其中包括迄今为止完全测序的 63 个种（致病/非致病）。这些包括 13 种不同的 RNases，其中 5 种是外切核酸酶（RNase PH、PNPase、RNase D、nano-RNases 和 RNase AS），8 种是内切核酸酶（RNase J、RNase H、RNase P、RNase III、RNase BN、RNase Z、RNase G 和 RNase E），尽管后来发现 RNase J 和 RNase BN 也具有外切核糖核酸酶功能。在这里，我们详细比较了大肠杆菌和分枝杆菌的 RNases，包括它们的类型、系统发育、结构、功能、调节和作用机制，主要集中在 RNase E 上。在这 13 种不同的分枝杆菌 RNases 中，有 10 种对细胞存活至关重要，且具有多样化的结构，因此它们是很有前途的药物靶点。RNase E 也是一种必需的内切核酸酶，在许多细菌中含量丰富，形成控制中心 RNA 加工/降解的 RNA 降解体复合物，并且在其 RNase 结构域中具有保守的 5' 传感器结构域/DNase-I 样区域。必需的分枝杆菌 RNases，特别是 RNase E，提供了一个潜在的药物靶点 repertoire，可以用于针对许多致命性分枝杆菌病的抑制剂/调节剂筛选。
