Biology of RNA damage and repair

摘要 每个核糖上独特的2‘-羟基(OH)基团使RNA很容易成为一些 内切酶，破坏RNA，产生5‘-羟基和2’，3‘-环的产物 磷酸盐末端。比如DNA修复系统，它可以监视和修复 为了保护基因组的遗传密码，RNA损伤的产物是 偶联末端修饰和加工步骤，包括连接、稳定和 退化。然而，与DNA损伤反应不同，我们才刚刚开始 了解RNA切割、末端修饰和加工是如何集成的，以及 “RNA损伤反应”如何共同促进RNA的加工和协调 监管控制。在这个MIRA中，我们继续探索RNA损伤和 修复，集中在4个具体问题上：1.人激酶的RNA靶标是什么？ 2.3‘端偶联修饰和3’⟶5‘RNA衰变控制rna 细菌RTC RNA修复的靶点和生理作用是什么？ 酶？4.2‘-磷酸修饰如何抑制核酸外切酶降解？

ABSTRACT Distinctive 2′-hydroxyl (OH) groups on every ribose make RNA an easy target of some endonucleases, which damage RNA, creating products with 5′-OH and 2′,3′-cyclic phosphate termini. Like DNA repair systems that surveil and repair lesions in the genome to preserve the genetic code, the products of RNA damage are substrates for coupled end modification and processing steps including ligation, stabilization, and degradation. However, unlike the DNA damage response, we are only beginning to understand how RNA cleavage, end modification, and processing are integrated, and how together the “RNA damage response” promotes RNA processing and orchestrates regulatory control. In this MIRA, we continue to explore the role of RNA damage and repair, focusing on 4 specific questions: 1. What are the RNA targets of human kinase- mediated decay?; 2. Do coupled 3′-end modification and 3′⟶5′ RNA decay control RNA fate?; 3. What are the targets and physiological roles of bacterial Rtc RNA repair enzymes? 4. How do 2′-phosphate modifications inhibit exonuclease degradation?