title: CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells.
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.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.
authors.forename: S John
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.|Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.|California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94143, USA.|Center for RNA Systems Biology, University of California, San Francisco, CA 94143, USA.
authors.forename: Max A
authors.initials: MA
authors.lastname: Horlbeck
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.
authors.forename: Harjus S
authors.initials: HS
authors.lastname: Birk
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Malatesta
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Attenello
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.|Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.|California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94143, USA.|Center for RNA Systems Biology, University of California, San Francisco, CA 94143, USA.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Villalta
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.|Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.|California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94143, USA.|Center for RNA Systems Biology, University of California, San Francisco, CA 94143, USA.
authors.forename: Min Y
authors.initials: MY
authors.lastname: Cho
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.|Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.|California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94143, USA.|Center for RNA Systems Biology, University of California, San Francisco, CA 94143, USA.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Mandegar
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Olvera
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.|Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.|California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94143, USA.|Center for RNA Systems Biology, University of California, San Francisco, CA 94143, USA.
authors.forename: Luke A
authors.initials: LA
authors.lastname: Gilbert
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.|Deparment of Medicine, University of California, San Francisco, CA 94143, USA.|Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Conklin
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA. daniel.lim@ucsf.edu jonathan.weissman@ucsf.edu.|Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.|California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94143, USA.|Center for RNA Systems Biology, University of California, San Francisco, CA 94143, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Weissman
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA. daniel.lim@ucsf.edu jonathan.weissman@ucsf.edu.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.|San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lim
mesh_terms: D048708:Cell Growth Processes / Q000235:genetics; D002460:Cell Line; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D056426:Genetic Loci; D005820:Genetic Testing; D015894:Genome, Human; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D000069550:Machine Learning; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D062085:RNA, Long Noncoding