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?

NARRATIVE RNA damage is created by endonuclease cleavage and often leads to RNA ligation, degradation, or stabilization. Several RNA repair enzymes have important roles in RNA metabolism, host-pathogen conflicts, and tissue development, but we do not understand how the dysregulation RNA damage and repair causes disease.