Multiple Quality Control Checkpoints Safeguard Small Nuclear RNA Biogenesis and Prevent Assembly of Aberrant Spliceosomes.

ABSTRACT: Defective small nuclear (sn)RNAs are produced from hundreds of human snRNA pseudogenes and mutant snRNA genes associated with human developmental disorders. Machineries that prevent defective snRNAs from disrupting pre-mRNA splicing remain poorly defined. Here, we identify multiple checkpoints in snRNA biogenesis monitored by quality control machineries that subject defective snRNAs to degradation and prevent their assembly into spliceosomes. We show that variant U1 snRNAs produced from human pseudogenes, some at rates approaching the canonical snRNAs, are impaired in 3' cleavage and targeted for degradation by the NEXT-exosome while failures in subsequent protein assembly steps promote NEXT-exosome- or Terminal Uridylyl Transferase 4/7-mediated degradation. These pathways also repress mut

SUBMITTER: Ma T 

PROVIDER: S-EPMC12667742 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature