Abstract:
:Targeted gene regulation on a genome-wide scale is a powerful strategy for interrogating, perturbing, and engineering cellular systems. Here, we develop a method for controlling gene expression based on Cas9, an RNA-guided DNA endonuclease from a type II CRISPR system. We show that a catalytically dead Cas9 lacking endonuclease activity, when coexpressed with a guide RNA, generates a DNA recognition complex that can specifically interfere with transcriptional elongation, RNA polymerase binding, or transcription factor binding. This system, which we call CRISPR interference (CRISPRi), can efficiently repress expression of targeted genes in Escherichia coli, with no detectable off-target effects. CRISPRi can be used to repress multiple target genes simultaneously, and its effects are reversible. We also show evidence that the system can be adapted for gene repression in mammalian cells. This RNA-guided DNA recognition platform provides a simple approach for selectively perturbing gene expression on a genome-wide scale.
journal_name
Celljournal_title
Cellauthors
Qi LS,Larson MH,Gilbert LA,Doudna JA,Weissman JS,Arkin AP,Lim WAdoi
10.1016/j.cell.2013.02.022subject
Has Abstractpub_date
2013-02-28 00:00:00pages
1173-83issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(13)00211-0journal_volume
152pub_type
杂志文章相关文献
CELL文献大全abstract::Two-pore domain (K2P) K(+) channels are major regulators of excitability that endow cells with an outwardly rectifying background "leak" conductance. In some K2P channels, strong voltage-dependent activation has been observed, but the mechanism remains unresolved because they lack a canonical voltage-sensing domain. H...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2016.02.002
更新日期:2016-02-25 00:00:00
abstract::The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation a...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2020.10.036
更新日期:2020-11-25 00:00:00
abstract::Signal recognition particle (SRP), a small ribonucleoprotein required for targeting secretory proteins to the ER, has three known functions: signal recognition, elongation arrest, and translocation promotion. Because SRP is inactivated by the sulfhydryl alkylating reagent N-ethylmaleimide (NEM), we have attempted to e...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(88)90529-6
更新日期:1988-01-15 00:00:00
abstract::Three-dimensional structures of a native simian and reassortant rotavirus have been determined by electron cryomicroscopy and computer image processing. The structural features of the native virus confirm that the hemagglutinin spike is a dimer of VP4, substantiated by in vivo radiolabeling studies. Exchange of native...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(93)90516-s
更新日期:1993-08-27 00:00:00
abstract::Metazoan evolution involves increasing protein domain complexity, but how this relates to control of biological decisions remains uncertain. The Ras guanine nucleotide exchange factor (RasGEF) Sos1 and its adaptor Grb2 are multidomain proteins that couple fibroblast growth factor (FGF) signaling to activation of the R...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2013.01.056
更新日期:2013-02-28 00:00:00
abstract::The global financial crisis has hit biotech companies hard both in the US and Europe as venture capital dries up. Finding new sources of long-term financing for translating research into new therapeutics will be essential for maintaining innovation and new drug development by biotech companies. ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.07.026
更新日期:2009-08-07 00:00:00
abstract::In a 4-cell stage C. elegans embryo, signaling by the P2 blastomere induces anterior-posterior polarity in the adjacent EMS blastomere, leading to endoderm formation. We have taken genetic and reverse genetic approaches toward understanding the molecular basis for this induction. These studies have identified a set of...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)80531-0
更新日期:1997-08-22 00:00:00
abstract::A nutritious diet low in calories improves the health and extends the life span of rodents. Recent studies identified a gene, SIR2, which encodes an NAD-dependent deacetylase and may mediate the effects of calorie restriction. In this review, we discuss SIR2 genes and calorie restriction in the lower organisms yeast a...
journal_title:Cell
pub_type: 杂志文章,评审
doi:10.1016/j.cell.2005.01.029
更新日期:2005-02-25 00:00:00
abstract::The human epsilon-globin gene has a number of alternative transcription-initiation sites located upstream of the canonical mRNA cap site. In three nonerythroid cell lines, "leaky" epsilon-globin transcription occurs exclusively from one of these upstream sites, the -200 cap site. Using a transient expression assay, we...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(84)90495-1
更新日期:1984-09-01 00:00:00
abstract::RNA polymerase II (RNAPII) lies at the core of dynamic control of gene expression. Using 53 RNAPII point mutants, we generated a point mutant epistatic miniarray profile (pE-MAP) comprising ∼60,000 quantitative genetic interactions in Saccharomyces cerevisiae. This analysis enabled functional assignment of RNAPII subd...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2013.07.033
更新日期:2013-08-15 00:00:00
abstract::Excessive accumulation of neurofilaments in the cell bodies and proximal axons of motor neurons is a major pathological hallmark during the early stages of many human motor neuron diseases. To test directly the consequence of overexpression of the major neurofilament subunit NF-L, we produced transgenic mice that accu...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(93)90157-l
更新日期:1993-04-09 00:00:00
abstract::Junctions that connect the endoplasmic reticulum (ER) and the plasma membrane (PM) are unique yet ubiquitous subcellular compartments. Giordano et al. now report that extended synaptotagmins (E-Syts) promote their formation, providing fundamental insight into the molecular machinery controlling ER and plasma membrane ...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2013.05.054
更新日期:2013-06-20 00:00:00
abstract::The bHLH-ZIP protein Mad heterodimerizes with Max as a sequence-specific transcriptional repressor. Mad is rapidly induced upon differentiation, and the associated switch from Myc-Max to Mad-Max heterocomplexes seem to repress genes normally activated by Myc-Max. We have identified two related mammalian cDNAs that enc...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(95)90355-0
更新日期:1995-03-10 00:00:00
abstract::Pure primary mesenchymal cells from definitive streak stage chick embryos have been prepared free of epiblast and hypoblast cells. These cells have the potential in culture to differentiate into erythroid cells, beating heart muscle tissue, chondrocytes and epithelial cells. Transformation in vitro of pure primary mes...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(79)90320-9
更新日期:1979-08-01 00:00:00
abstract::V(D)J recombination of antigen receptor gene segments in B and T cells is mediated by the lymphoid-specific proteins RAG1 and RAG2. Now, Ji et al. (2010) demonstrate how RAG1 and RAG2 use DNA sequence specificity and modified histones within chromatin to target specific loci for V(D)J recombination at different stages...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2010.04.014
更新日期:2010-04-30 00:00:00
abstract::Fractionation of a microsomal detergent extract with ammonium sulfate allows separation of the signal recognition particle receptor (SR alpha), which is required for targeting of the nascent chain, from other microsomal proteins, such as signal peptidase, whose activity is displayed during subsequent translocation. Th...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(91)90091-c
更新日期:1991-05-17 00:00:00
abstract::Initiation of tumorigenesis in mouse skin can be accomplished by mutagenesis of the H-ras gene by treatment with chemical carcinogens. A mouse model system has been developed to study the additional genetic events that take place during tumor progression. Skin carcinomas were induced in F1 hybrid mice exhibiting restr...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(90)90523-h
更新日期:1990-05-04 00:00:00
abstract::Autophagy is a catabolic process in which lysosomes degrade intracytoplasmic contents transported in double-membraned autophagosomes. Autophagosomes are formed by the elongation and fusion of phagophores, which can be derived from preautophagosomal structures coming from the plasma membrane and other sites like the en...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2011.06.023
更新日期:2011-07-22 00:00:00
abstract::In vertebrates, muscles of the limbs and body wall derive from the lateral compartment of the embryonic somites, and axial muscles derive from the medial compartment. Whereas the mechanisms that direct patterning of somites along the dorsoventral axis are beginning to be understood, little is known about the tissue in...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)81291-x
更新日期:1996-02-09 00:00:00
abstract::Organisms maintain the correct balance of intracellular metals primarily through metal-sensing proteins that control transport and storage of the target ion(s). Here, we reveal the basis of metal sensing and genetic control by a metalloregulatory RNA. Our data demonstrate that a previously uncharacterized orphan ribos...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2007.06.051
更新日期:2007-09-07 00:00:00
abstract::Twitter needs no introduction. This "microblogging" service has gained tremendous popularity in the 2 years since its launch. Yet, most scientists are steering clear of it. Laura Bonetta speaks to some who have found value in tweeting. ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2009.10.017
更新日期:2009-10-30 00:00:00
abstract::The mTORC1 kinase is a master growth regulator that senses many environmental cues, including amino acids. Activation of mTORC1 by arginine requires SLC38A9, a poorly understood lysosomal membrane protein with homology to amino acid transporters. Here, we validate that SLC38A9 is an arginine sensor for the mTORC1 path...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2017.09.046
更新日期:2017-10-19 00:00:00
abstract::Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2014.03.049
更新日期:2014-04-24 00:00:00
abstract::We propose a mechanism for the priming of influenza viral RNA transcription by capped RNAs in which specific 5'-terminal fragments are cleaved from the capped RNAs by a virion-associated endonuclease. These fragments would serve as the actual primers for the initiation of transcription by the initial incorporation by ...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(81)90449-9
更新日期:1981-03-01 00:00:00
abstract::Muscle atrophy (cachexia) in cancer patients is a life-threatening condition for which therapeutic options are limited. Zhou et al. (2010) now identify a new target for treating cachexia, the activin type-2 receptor (ActRIIB). In several mouse models of cachexia, the authors reversed wasting of skeletal and cardiac mu...
journal_title:Cell
pub_type: 评论,杂志文章
doi:10.1016/j.cell.2010.08.004
更新日期:2010-08-20 00:00:00
abstract::The small molecular weight RNAs of the HeLa cell have been located in specific subcellular fractions. SnA is located in the nucleolus and is partially bonded to nucleolar 28S RNA. SnD, the most abundant of the small nuclear RNAs, is partially released from the nucleus when the nuclear preparation is briefly warmed. Sn...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(76)90181-1
更新日期:1976-05-01 00:00:00
abstract::In 1981, the acquired immunodeficiency syndrome (AIDS) appeared insidiously and mystified doctors and scientists alike. No one could have predicted then that it would become, arguably, the worst plague in human history. Today, 33 million persons are living with infection by the human immunodeficiency virus type 1 (HIV...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2008.05.003
更新日期:2008-05-16 00:00:00
abstract::Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tiss...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/j.cell.2014.12.021
更新日期:2015-01-15 00:00:00
abstract::Treatment of guinea pig neutrophils with pertussis toxin (islet-activating protein; IAP) results in inhibition of N-formyl peptide receptor-mediated release of arachidonic acid and granular enzymes. Inhibition by the toxin is specific, in that responses to the calcium ionophore A23187 are not affected. The action of t...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/0092-8674(84)90008-4
更新日期:1984-12-01 00:00:00
abstract::Angiogenesis is an important event for embryonic organogenesis as well as for tissue repair in the adult. Here, we show that hematopoietic stem cells (HSCs) play important roles for angiogenesis during embryogenesis. To investigate the role of HSCs in endothelial cell (EC) development, we analyzed AML1-deficient embry...
journal_title:Cell
pub_type: 杂志文章
doi:10.1016/s0092-8674(00)00025-8
更新日期:2000-07-21 00:00:00