Integrative and accurate annotations enhance current nonsense-mediated mRNA decay rules.

ABSTRACT: Variants generating premature termination codons (PTCs) are a major cause of human genetic disease, and it is crucial to accurately assess their impact. Nonsense-mediated mRNA decay (NMD) is a surveillance system that degrades mRNAs containing PTCs to prevent the production of truncated proteins. Prior studies have shown that PTC position-dependent rules are major contributors to NMD efficiency, though they leave a portion of the variability unexplained. To improve the coverage of current NMD escape rules, we used matched human genome and transcriptome data from 1086 individuals and re-evaluated NMD efficiency by considering multi-nucleotide variants (MNVs), translation status, and RNA isoform expression as part of an accurate annotation. Integrated data assessment and accurate annotation

SUBMITTER: Iha H 

PROVIDER: S-EPMC12668785 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature