CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies.

ABSTRACT:

Introduction

Genes contain multiple promoters that can drive the expression of various transcript isoforms. Although transcript isoforms from the same gene could have diverse and non-overlapping functions, current loss-of-function methodologies are not able to differentiate between isoform-specific phenotypes.

Results

Here, we show that CRISPR interference (CRISPRi) can be adopted for targeting specific promoters within a gene, enabling isoform-specific loss-of-function genetic screens. We use this strategy to test functional dependencies of 820 transcript isoforms that are gained in gastric cancer (GC). We identify a subset of GC-gained transcript isoform dependencies, and of these, we validate CIT kinase as a novel GC dependency. We further show that some genes express iso

SUBMITTER: Davies R 

PROVIDER: S-EPMC7836456 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature