Apoptosis Research Centre, University of Galway, Galway, Ireland.
School of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
Cell Mol Life Sci. 2023 Nov 7;80(12):352. doi: 10.1007/s00018-023-05001-5.
To be functional, some RNAs require a processing step involving splicing events. Each splicing event necessitates an RNA ligation step. RNA ligation is a process that can be achieved with various intermediaries such as self-catalysing RNAs, 5'-3' and 3'-5' RNA ligases. While several types of RNA ligation mechanisms occur in human, RtcB is the only 3'-5' RNA ligase identified in human cells to date. RtcB RNA ligation activity is well known to be essential for the splicing of XBP1, an essential transcription factor of the unfolded protein response; as well as for the maturation of specific intron-containing tRNAs. As such, RtcB is a core factor in protein synthesis and homeostasis. Taking advantage of the high homology between RtcB orthologues in archaea, bacteria and eukaryotes, this review will provide an introduction to the structure of RtcB and the mechanism of 3'-5' RNA ligation. This analysis is followed by a description of the mechanisms regulating RtcB activity and localisation, its known partners and its various functions from bacteria to human with a specific focus on human cancer.
为了实现功能，一些 RNA 需要经历一个涉及剪接事件的处理步骤。每个剪接事件都需要一个 RNA 连接步骤。RNA 连接是一种可以通过各种中间产物实现的过程，如自我催化的 RNA、5'-3' 和 3'-5' RNA 连接酶。虽然人类中存在几种类型的 RNA 连接机制，但截至目前，RtcB 是唯一在人类细胞中鉴定出的 3'-5' RNA 连接酶。RtcB RNA 连接活性对于 XBP1 的剪接至关重要，XBP1 是未折叠蛋白反应的必需转录因子；同时对于特定内含子 tRNA 的成熟也是必需的。因此，RtcB 是蛋白质合成和内稳态的核心因素。利用古菌、细菌和真核生物中 RtcB 同源物之间的高度同源性，本综述将介绍 RtcB 的结构和 3'-5' RNA 连接的机制。在这一分析之后，将描述调节 RtcB 活性和定位的机制、其已知的伴侣以及从细菌到人各种已知的功能，特别关注人类癌症。
