Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA.
Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA.
DNA Repair (Amst). 2019 Sep;81:102653. doi: 10.1016/j.dnarep.2019.102653. Epub 2019 Jul 8.
Cells utilize sophisticated RNA processing machines to ensure the quality of RNA. Many RNA processing machines have been further implicated in regulating the DNA damage response signifying a strong link between RNA processing and genome maintenance. One of the most intricate and highly regulated RNA processing pathways is the processing of the precursor ribosomal RNA (pre-rRNA), which is paramount for the production of ribosomes. Removal of the Internal Transcribed Spacer 2 (ITS2), located between the 5.8S and 25S rRNA, is one of the most complex steps of ribosome assembly. Processing of the ITS2 is initiated by the newly discovered endoribonuclease Las1, which cleaves at the C2 site within the ITS2, generating products that are further processed by the polynucleotide kinase Grc3, the 5'→3' exonuclease Rat1, and the 3'→5' RNA exosome complex. In addition to their defined roles in ITS2 processing, these critical cellular machines participate in other stages of ribosome assembly, turnover of numerous cellular RNAs, and genome maintenance. Here we summarize recent work defining the molecular mechanisms of ITS2 processing by these essential RNA processing machines and highlight their emerging roles in transcription termination, heterochromatin function, telomere maintenance, and DNA repair.
细胞利用复杂的 RNA 处理机器来确保 RNA 的质量。许多 RNA 处理机器进一步被牵连到调节 DNA 损伤反应中，这表明 RNA 处理和基因组维护之间存在很强的联系。最复杂和高度调控的 RNA 处理途径之一是前体核糖体 RNA（pre-rRNA）的处理，这对于核糖体的产生至关重要。核糖体组装过程中最复杂的步骤之一是去除位于 5.8S 和 25S rRNA 之间的内部转录间隔区 2（ITS2）。ITS2 的加工是由新发现的内切核酸酶 Las1 启动的，它在 ITS2 内的 C2 位点切割，生成的产物进一步由多核苷酸激酶 Grc3、5'→3'外切核酸酶 Rat1 和 3'→5'RNA 外切体复合物处理。除了它们在 ITS2 加工中的明确作用外，这些关键的细胞机器还参与核糖体组装、许多细胞 RNA 的周转以及基因组维护的其他阶段。在这里，我们总结了最近的工作，定义了这些必需的 RNA 处理机器对 ITS2 加工的分子机制，并强调了它们在转录终止、异染色质功能、端粒维持和 DNA 修复中的新兴作用。
