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CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells SCIENCE Liu, S. J., Horlbeck, M. A., Cho, S. W., Birk, H. S., Malatesta, M., He, D., Attenello, F. J., Villalta, J. E., Cho, M. Y., Chen, Y., Mandegar, M. A., Olvera, M. P., Gilbert, L. A., Conklin, B. R., Chang, H. Y., Weissman, J. S., Lim, D. A. 2017; 355 (6320)

Abstract

The human genome produces thousands of long noncoding RNAs (lncRNAs)-transcripts >200 nucleotides long that do not encode proteins. Although critical roles in normal biology and disease have been revealed for a subset of lncRNAs, the function of the vast majority remains untested. We developed a CRISPR interference (CRISPRi) platform targeting 16,401 lncRNA loci in seven diverse cell lines, including six transformed cell lines and human induced pluripotent stem cells (iPSCs). Large-scale screening identified 499 lncRNA loci required for robust cellular growth, of which 89% showed growth-modifying function exclusively in one cell type. We further found that lncRNA knockdown can perturb complex transcriptional networks in a cell type-specific manner. These data underscore the functional importance and cell type specificity of many lncRNAs.

View details for DOI 10.1126/science.aah7111

View details for Web of Science ID 000391739900002

View details for PubMedID 27980086

View details for PubMedCentralID PMC5394926