期刊
SCIENCE
卷 355, 期 6320, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aah7111
关键词
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资金
- NIH [1R01NS091544-01A1, F30 NS092319-01, P50 GM102706, U01 CA168370, R01 DA036858, R35-CA209919, P50-HG007735, U01HL100406, P01HL089707, R01HL130533]
- VA grant [5I01 BX000252-07]
- NIH Specialized Programs of Research Excellence Developmental Research Program subaward
- Shurl and Kay Curci Foundation
- LoGlio Foundation
- Hana Jabsheh Initiative
- Howard Hughes Medical Institutes
- Gladstone Institutes
- NIH/NCI Pathway to Independence Award [K99CA204602]
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.
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