Genetic and functional analysis of unproductive splicing using LeafCutter2.

ABSTRACT: Alternative splicing commonly generates unproductive mRNA transcripts that harbor premature termination codons¹, leading to their degradation by nonsense-mediated decay (NMD). These events reduce overall protein expression levels of affected genes, potentially contributing to gene regulation and disease mechanisms. Here, we present LeafCutter2, which enables identification and quantification of unproductive splicing from short-read RNA-seq data. LeafCutter2 requires minimal gene annotations (start and stop codons) to annotate NMD-inducing splicing events, and identifies differential unproductive splicing between groups, providing insights into its contributions to differential gene expression. Moreover, LeafCutter2 enables mapping of unproductive splicing quantitative trait loci

SUBMITTER: Najar CFBA 

PROVIDER: S-EPMC12026817 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature