CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion

Genome Biol. 2017 Jun 14;18(1):108. doi: 10.1186/s13059-017-1237-8.

Abstract

CRISPR is widely used to disrupt gene function by inducing small insertions and deletions. Here, we show that some single-guide RNAs (sgRNAs) can induce exon skipping or large genomic deletions that delete exons. For example, CRISPR-mediated editing of β-catenin exon 3, which encodes an autoinhibitory domain, induces partial skipping of the in-frame exon and nuclear accumulation of β-catenin. A single sgRNA can induce small insertions or deletions that partially alter splicing or unexpected larger deletions that remove exons. Exon skipping adds to the unexpected outcomes that must be accounted for, and perhaps taken advantage of, in CRISPR experiments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • CRISPR-Cas Systems*
  • Exons / genetics*
  • Gene Editing*
  • Genome, Human / genetics*
  • Humans
  • RNA, Guide / genetics
  • Sequence Deletion
  • beta Catenin / genetics

Substances

  • CTNNB1 protein, human
  • RNA, Guide
  • beta Catenin