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Updated: Oct 26, 2026

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
Published on: September 15, 2021
Genetic Variation Disrupts RNA Structural Repression of Cryptic Splice Sites
Abstract:
Interpreting how genetic variants alter RNA processing remains a major challenge in human genetics. Using Framingham Heart Study data and genome-wide and mutational analyses, we show that G-tract-disrupting variants activate cryptic 3' splice sites in association with predicted local RNA structural destabilization, while compensatory mutations restoring structural stability re-establish splicing repression. Approximately 1.6 million such sites occur genome-wide, revealing RNA structural disruption as a candidate mechanism of variant-induced cryptic splicing.
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