CRISPR-dCas13 Modulates Alternative Splicing

The study highlights the efficacy of the dCasRx variant of dCas13, which influences exon inclusion levels when directed at specific splice sites, allowing for isoform-switching in human cell lines. Moreover, it advances the understanding of splicing mechanisms in physiological and disease contexts.

dCas13 achieves alternative splicing by targeting specific RNA splice sites or regulatory elements with guide RNAs. This interfering with the splicing machinery modulates exon inclusion or exclusion without affecting overall gene expression.

In particular, they revealed the role of cis-regulatory RNA elements in determining splicing outcomes, with dCasRx showing high specificity in its effects. The tool also successfully pinpointed key splicing elements, such as exonic splicing enhancers and silencers, further proving its value for functional RNA studies.

The study was led by Yaiza Núñez-Álvarez and Reini F. Luco at Université de Montpellier, and it was published in Nucleic Acids Research on 20 August 2024.