U2AF1 mutations may reverse harmful gene skipping caused by KRAS mutations

Mutations in the U2AF1 gene can reverse splicing defects caused by specific KRAS mutations in lung adenocarcinoma.

• A KRAS mutation (G12S) resulted in skipping of KRAS exon 2, creating a nonfunctional transcript.
• Expression of the U2AF1^S34F mutant restored KRAS function by preventing exon skipping.
• U2AF1^S34F mutations were enriched in lung adenocarcinomas with KRAS^G12S mutations.
• Analysis showed significant coenrichment of KRAS^Q61R and U2AF1^I24T mutations in cancer genomes.
• KRAS^Q61R mutation caused skipping of KRAS exon 3, which could be rescued by U2AF1^I24T expression.

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