Sm complex assembly and 5′ cap trimethylation promote selective processing of snRNAs by the 3′ exonuclease TOE1

• 成果类型: Article
• 署名作者: Ma, Tiantai; Xiong, Erica S.; Lardelli, Rea M.; Lykke- Andersen, Jens
• 署名单位: University of California System; University of California San Diego
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13752
• DOI: 10.1073/pnas.2315259121
• 发表日期: 2024-01-16
• 关键词: small-nuclear-rna; small nucleolar rnas; poly(a)-specific ribonuclease; telomerase rna; surveillance pathway; gene-expression; messenger-rna; u1 snrnas; protein; parn

摘要

Competing exonucleases that promote 3 ' end maturation or degradation direct quality control of small non- coding RNAs, but how these enzymes distinguish normal from aberrant RNAs is poorly understood. The Pontocerebellar Hypoplasia 7 (PCH7)-associated 3 ' exonuclease TOE1 promotes maturation of canonical small nuclear RNAs (snRNAs). Here, we demonstrate that TOE1 achieves specificity toward canonical snRNAs through their Sm complex assembly and cap trimethylation, two features that distinguish snRNAs undergoing correct biogenesis from other small non- coding RNAs. Indeed, disruption of Sm complex assembly via snRNA mutations or protein depletions obstructs snRNA processing by TOE1, and in vitro snRNA processing by TOE1 is stimulated by a tri-methylated cap. An unstable snRNA variant that normally fails to undergo maturation becomes fully processed by TOE1 when its degenerate Sm binding motif is converted into a canonical one. Our findings uncover the molecular basis for how TOE1 distinguishes snRNAs from other small non- coding RNAs and explain how TOE1 promotes maturation specifically of canonical snRNAs undergoing proper processing.