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dc.titleCRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies
dc.contributor.authorDavies, Rebecca
dc.contributor.authorLiu, Ling
dc.contributor.authorTaotao, Sheng
dc.contributor.authorTuano, Natasha
dc.contributor.authorChaturvedi, Richa
dc.contributor.authorHuang, Kie Kyon
dc.contributor.authorItman, Catherine
dc.contributor.authorMandoli, Amit
dc.contributor.authorQamra, Aditi
dc.contributor.authorHu, Changyuan
dc.contributor.authorPowell, David
dc.contributor.authorDaly, Roger J.
dc.contributor.authorTan, Patrick
dc.contributor.authorRosenbluh, Joseph
dc.identifier.citationDavies, Rebecca, Liu, Ling, Taotao, Sheng, Tuano, Natasha, Chaturvedi, Richa, Huang, Kie Kyon, Itman, Catherine, Mandoli, Amit, Qamra, Aditi, Hu, Changyuan, Powell, David, Daly, Roger J., Tan, Patrick, Rosenbluh, Joseph (2021-01-26). CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies. Genome Biology 22 (1) : 47. ScholarBank@NUS Repository.
dc.description.abstractIntroduction: 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 isoforms with opposite functions. Specifically, we find that the tumour suppressor ZFHX3 expresses an isoform that has a paradoxical oncogenic role that correlates with poor patient outcome. Conclusions: Our work finds isoform-specific phenotypes that would not be identified using current loss-of-function approaches that are not designed to target specific transcript isoforms. © 2021, The Author(s).
dc.publisherBioMed Central Ltd
dc.rightsAttribution 4.0 International
dc.sourceScopus OA2021
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.sourcetitleGenome Biology
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