Endonucleolytic cleavage is the primary mechanism of decay elicited by <i>C. elegans</i> nonsense-mediated mRNA decay.

ABSTRACT: Premature stop codon-containing mRNAs can produce truncated and dominantly acting proteins that harm cells. Eukaryotic cells protect themselves by degrading such mRNAs via the nonsense-mediated mRNA decay (NMD) pathway. The precise reactions by which cells attack NMD-target mRNAs remain obscure, precluding a biochemical understanding of NMD and hampering therapeutic efforts to control NMD. Here, we modify and deploy single-molecule nanopore mRNA sequencing to clarify the route by which NMD targets are attacked in an animal. We obtain single-molecule measures of splicing isoform, cleavage state, and poly(A) tail length. We observe robust endonucleolytic cleavage of NMD targets in vivo that depends on the nuclease SMG-6. We show that NMD-target mRNAs experience deadenylation and decapping, s

SUBMITTER: Viscardi MJ 

PROVIDER: S-EPMC12129023 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature