Multiple quality control checkpoints safeguard small nuclear RNA biogenesis and prevent assembly of aberrant spliceosomes.

Multiple quality control checkpoints in human snRNA biogenesis degrade defective U1 snRNAs and block their spliceosome assembly, preventing aberrant spliceosomes and altered pre-mRNA splicing.

• Why it matters: Defective snRNAs from human pseudogenes and mutant genes can disrupt pre-mRNA splicing, but the quality-control mechanisms preventing this are not well defined.
• What they did: The study mapped checkpoints where impaired 3' cleavage triggers NEXT-exosome degradation, and failures in protein assembly promote NEXT-exosome- or TUT4/7-mediated degradation of variant U1 snRNAs.
• The result: Blocking snRNA quality control causes aberrant spliceosome formation and altered pre-mRNA splicing, while these pathways also repress mutant snRNAs linked to human developmental disorders.

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