From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II.


: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 subdomains and uncovered connections between individual regions and other protein complexes. Using splicing microarrays and mutants that alter elongation rates in vitro, we found an inverse relationship between RNAPII speed and in vivo splicing efficiency. Furthermore, the pE-MAP classified fast and slow mutants that favor upstream and downstream start site selection, respectively. The striking coordination of polymerization rate with transcription initiation and splicing suggests that transcription rate is tuned to regulate multiple gene expression steps. The pE-MAP approach provides a powerful strategy to understand other multifunctional machines at amino acid resolution.






Braberg H,Jin H,Moehle EA,Chan YA,Wang S,Shales M,Benschop JJ,Morris JH,Qiu C,Hu F,Tang LK,Fraser JS,Holstege FC,Hieter P,Guthrie C,Kaplan CD,Krogan NJ




Has Abstract


2013-08-15 00:00:00
















  • Cyclic dinucleotides and the innate immune response.

    abstract::Cyclic dinucleotides (CDNs) have been previously recognized as important secondary signaling molecules in bacteria and, more recently, in mammalian cells. In the former case, they represent secondary messengers affecting numerous responses of the prokaryotic cell, whereas in the latter, they act as agonists of the inn...


    pub_type: 杂志文章,评审


    authors: Danilchanka O,Mekalanos JJ

    更新日期:2013-08-29 00:00:00

  • Structural rearrangement of ebola virus VP40 begets multiple functions in the virus life cycle.

    abstract::Proteins, particularly viral proteins, can be multifunctional, but the mechanisms behind multifunctionality are not fully understood. Here, we illustrate through multiple crystal structures, biochemistry, and cellular microscopy that VP40 rearranges into different structures, each with a distinct function required for...


    pub_type: 杂志文章


    authors: Bornholdt ZA,Noda T,Abelson DM,Halfmann P,Wood MR,Kawaoka Y,Saphire EO

    更新日期:2013-08-15 00:00:00

  • A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits.

    abstract::Multiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCH...


    pub_type: 杂志文章


    authors: Almeida-Souza L,Frank RAW,García-Nafría J,Colussi A,Gunawardana N,Johnson CM,Yu M,Howard G,Andrews B,Vallis Y,McMahon HT

    更新日期:2018-07-12 00:00:00

  • Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-PtdIns(3,4,5)P3 interactions.

    abstract::Inositol phosphates are well-known signaling molecules, whereas the inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (InsP7/IP7) and bis-diphosphoinositol tetrakisphosphate (InsP8/IP8), are less well characterized. We demonstrate physiologic regulation of Dictyostelium chemotaxis by InsP7 mediated ...


    pub_type: 杂志文章


    authors: Luo HR,Huang YE,Chen JC,Saiardi A,Iijima M,Ye K,Huang Y,Nagata E,Devreotes P,Snyder SH

    更新日期:2003-09-05 00:00:00

  • Expression cloning of an activin receptor, a predicted transmembrane serine kinase.

    abstract::Activins are involved in the regulation of multiple biological events, ranging from early development to pituitary function. To characterize the cellular mechanisms involved in these processes, cDNAs coding for an activin receptor were cloned from AtT20 mouse corticotropic cells by screening COS cell transfectants for...


    pub_type: 杂志文章


    authors: Mathews LS,Vale WW

    更新日期:1991-06-14 00:00:00

  • Transepithelial projections from basal cells are luminal sensors in pseudostratified epithelia.

    abstract::Basal cells are by definition located on the basolateral side of several epithelia, and they have never been observed reaching the lumen. Using high-resolution 3D confocal imaging, we report that basal cells extend long and slender cytoplasmic projections that not only reach toward the lumen but can cross the tight ju...


    pub_type: 杂志文章


    authors: Shum WW,Da Silva N,McKee M,Smith PJ,Brown D,Breton S

    更新日期:2008-12-12 00:00:00

  • Folding and trimerization of clathrin subunits at the triskelion hub.

    abstract::The triskelion shape of the clathrin molecule enables it to form the polyhedral protein network that covers clathrin-coated pits and vesicles. Domains within the clathrin heavy chain that are responsible for maintaining triskelion shape and function were identified and localized. Sequences that mediate trimerization a...


    pub_type: 杂志文章


    authors: Näthke IS,Heuser J,Lupas A,Stock J,Turck CW,Brodsky FM

    更新日期:1992-03-06 00:00:00

  • The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family.

    abstract::The surface glycoproteins T4 and T8 define different functional subsets of T lymphocytes and may act as recognition molecules mediating appropriate interactions between the T cell and its target. Previously we employed gene transfer and subtractive hybridization to isolate a T8 cDNA; now we have isolated and sequenced...


    pub_type: 杂志文章


    authors: Maddon PJ,Littman DR,Godfrey M,Maddon DE,Chess L,Axel R

    更新日期:1985-08-01 00:00:00

  • p53 regulation orchestrates the TGF-beta response.

    abstract::Among its multiple functions, p53 is a critical regulator of TGF-beta responses. Sasai et al. (2008) now identify a new p53 inhibitory protein, XFDL156. During embryonic development, this factor is expressed in the ectoderm germ layer and maintains the pluripotency of ectodermal cells by inhibiting TGF-beta target gen...


    pub_type: 评论,杂志文章


    authors: Piccolo S

    更新日期:2008-05-30 00:00:00

  • Identification of early replicating fragile sites that contribute to genome instability.

    abstract::DNA double-strand breaks (DSBs) in B lymphocytes arise stochastically during replication or as a result of targeted DNA damage by activation-induced cytidine deaminase (AID). Here we identify recurrent, early replicating, and AID-independent DNA lesions, termed early replication fragile sites (ERFSs), by genome-wide l...


    pub_type: 杂志文章,评审


    authors: Barlow JH,Faryabi RB,Callén E,Wong N,Malhowski A,Chen HT,Gutierrez-Cruz G,Sun HW,McKinnon P,Wright G,Casellas R,Robbiani DF,Staudt L,Fernandez-Capetillo O,Nussenzweig A

    更新日期:2013-01-31 00:00:00

  • A major step on the road to understanding a unique posttranslational modification and its role in a genetic disease.

    abstract::The posttranslational conversion of cysteine to C(alpha)-formylglycine in the catalytic site of mammalian sulfatases is deficient in the rare but devastating disorder multiple sulfatase deficiency (MSD). Two papers in this issue of Cell report the cloning of a gene responsible for this activity. ...


    pub_type: 评论,杂志文章,评审


    authors: Baenziger JU

    更新日期:2003-05-16 00:00:00

  • Genetic evidence that Tn10 transposes by a nonreplicative mechanism.

    abstract::We present genetic evidence that the tetracycline resistance element Tn10 transposes by a nonreplicative mechanism. Heteroduplex Tn10 elements containing three single base pair mismatches were constructed on lambda phage genomes and allowed to transpose from lambda into the bacterial chromosome. Analysis of TetR colon...


    pub_type: 杂志文章


    authors: Bender J,Kleckner N

    更新日期:1986-06-20 00:00:00

  • Cis-acting induction of adenovirus transcription.

    abstract::At early times after adenovirus infection, transcription from all early viral promoters requires the expression of a 289 amino acid phosphoprotein encoded in the pre-early transcription unit E1A. Mutations in E1A result in a marked delay in the induction of early viral transcription. To distinguish between possible mo...


    pub_type: 杂志文章


    authors: Gaynor RB,Berk AJ

    更新日期:1983-07-01 00:00:00

  • TB or Not TB: how Mycobacterium tuberculosis may evade drug treatment.

    abstract::In this issue of Cell, a study by Valerie Mizrahi and her colleagues suggests that a putative error-prone DNA polymerase encoded by the dnaE2 gene of Mycobacterium tuberculosis may bypass certain types of DNA base damage, generating mutations. This may be an important mechanism for generating drug-resistant strains of...


    pub_type: 评论,杂志文章,评审


    authors: Friedberg EC,Fischhaber PL

    更新日期:2003-04-18 00:00:00

  • Reduced temperature prevents transfer of a membrane glycoprotein to the cell surface but does not prevent terminal glycosylation.

    abstract::The transport kinetics of the influenza virus hemagglutinin from its site of synthesis to the apical plasma membrane of Madin-Darby canine kidney cells, a polarized epithelial cell line, were studied by a sensitive tryptic assay. Hemagglutinin acquired terminal sugars, as judged by sensitivity to endo-beta-N-acetylglu...


    pub_type: 杂志文章


    authors: Matlin KS,Simons K

    更新日期:1983-08-01 00:00:00

  • The biological and chemical basis for tissue-selective amyloid disease.

    abstract::Factors controlling the onset and progression of extracellular amyloid diseases remain largely unknown. Central to disease etiology is the efficiency of the endoplasmic reticulum (ER) machinery that targets destabilized mutant proteins for degradation and the enhanced tendency of these variants to aggregate if secrete...


    pub_type: 杂志文章


    authors: Sekijima Y,Wiseman RL,Matteson J,Hammarström P,Miller SR,Sawkar AR,Balch WE,Kelly JW

    更新日期:2005-04-08 00:00:00

  • SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality.

    abstract::SOCS1 is an SH2-containing protein that is primarily expressed in thymocytes in a cytokine- and T cell receptor-independent manner. SOCS1 deletion causes perinatal lethality with death by 2-3 weeks. During this period thymic changes include a loss of cellularity and a switch from predominantly CD4+ CD8+ to single posi...


    pub_type: 杂志文章


    authors: Marine JC,Topham DJ,McKay C,Wang D,Parganas E,Stravopodis D,Yoshimura A,Ihle JN

    更新日期:1999-09-03 00:00:00

  • Sequence from early region of polyoma virus DNA containing viral replication origin and encoding small, middle and (part of) large T antigens.

    abstract::The sequence of about one third of the polyoma virus genome is presented. This sequence covers the origin of replication of two large plaque strains (A2 and A3) of polyoma virus. The two strains differ by 11 bp in the origin region. A model for replication is suggested. The sequence probably also covers the entire cod...


    pub_type: 杂志文章


    authors: Soeda E,Arrand JR,Smolar N,Griffin BE

    更新日期:1979-06-01 00:00:00

  • Critical role of amyloid-like oligomers of Drosophila Orb2 in the persistence of memory.

    abstract::A long-standing question in the study of long-term memory is how a memory trace persists for years when the proteins that initiated the process turn over and disappear within days. Previously, we postulated that self-sustaining amyloidogenic oligomers of cytoplasmic polyadenylation element-binding protein (CPEB) provi...


    pub_type: 杂志文章


    authors: Majumdar A,Cesario WC,White-Grindley E,Jiang H,Ren F,Khan MR,Li L,Choi EM,Kannan K,Guo F,Unruh J,Slaughter B,Si K

    更新日期:2012-02-03 00:00:00

  • Isolation, sequence analysis, and intron-exon arrangement of the gene encoding bovine rhodopsin.

    abstract::We have isolated cDNA clones generated from the mRNA encoding the opsin apoprotein of bovine rhodopsin and used these cDNAs to isolate genomic DNA clones containing the complete opsin gene. Nucleotide sequence analysis of the cloned DNAs has yielded a complete amino acid sequence for bovine rhodopsin and provided an i...


    pub_type: 杂志文章


    authors: Nathans J,Hogness DS

    更新日期:1983-10-01 00:00:00

  • Naturally Occurring Off-Switches for CRISPR-Cas9.

    abstract::CRISPR-Cas9 technology would be enhanced by the ability to inhibit Cas9 function spatially, temporally, or conditionally. Previously, we discovered small proteins encoded by bacteriophages that inhibit the CRISPR-Cas systems of their host bacteria. These "anti-CRISPRs" were specific to type I CRISPR-Cas systems that d...


    pub_type: 评论,杂志文章


    authors: Pawluk A,Amrani N,Zhang Y,Garcia B,Hidalgo-Reyes Y,Lee J,Edraki A,Shah M,Sontheimer EJ,Maxwell KL,Davidson AR

    更新日期:2016-12-15 00:00:00

  • Distinctive Activation Mechanism for Angiotensin Receptor Revealed by a Synthetic Nanobody.

    abstract::The angiotensin II (AngII) type 1 receptor (AT1R) is a critical regulator of cardiovascular and renal function and is an important model for studies of G-protein-coupled receptor (GPCR) signaling. By stabilizing the receptor with a single-domain antibody fragment ("nanobody") discovered using a synthetic yeast-display...


    pub_type: 杂志文章


    authors: Wingler LM,McMahon C,Staus DP,Lefkowitz RJ,Kruse AC

    更新日期:2019-01-24 00:00:00

  • Mechanism of formation of pseudotypes between vesicular stomatitis virus and murine leukemia virus.

    abstract::Pseudotypes of vesicular stomatitis virus (VSV) and Moloney murine leukemia virus (MuLV), defined by their resistance to neutralization by anti-VSV antiserum, are released preferentially at early times after infection of MuLV-producing cells with VSV. At later times, after synthesis of MuLV proteins has been inhibited...


    pub_type: 杂志文章


    authors: Witte ON,Baltimore D

    更新日期:1977-07-01 00:00:00

  • A single gene from yeast for both nuclear and cytoplasmic polyadenylate-binding proteins: domain structure and expression.

    abstract::Nuclear and cytoplasmic poly(A)-binding proteins have been purified from Saccharomyces cerevisiae, and antisera have been used to isolate a gene that encodes them. The gene occurs in a single copy on chromosome 5 and gives rise to a unique, unspliced 2.1 kb transcript. The nuclear protein appears to be derived from th...


    pub_type: 杂志文章


    authors: Sachs AB,Bond MW,Kornberg RD

    更新日期:1986-06-20 00:00:00

  • Androgen-dependent fibrinolytic activity in a murine mammary carcinoma (Shionogi SC-115 cells) in vitro.

    abstract::Physiological concentrations of dihydrotestosterone (DHT) can specifically induce the release of fibrinolysin from androgen-dependent mammary carcinoma (Shionogi SC-115) cells in vitro. No fibrinolytic activity was observed in cells cultured either in the absence of DHT or presence of pharmacological concentrations of...


    pub_type: 杂志文章


    authors: Mak TW,Rutledge G,Sutherland DJ

    更新日期:1976-02-01 00:00:00

  • Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat.

    abstract::Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and insulin resistance, al...


    pub_type: 杂志文章


    authors: Atanur SS,Diaz AG,Maratou K,Sarkis A,Rotival M,Game L,Tschannen MR,Kaisaki PJ,Otto GW,Ma MC,Keane TM,Hummel O,Saar K,Chen W,Guryev V,Gopalakrishnan K,Garrett MR,Joe B,Citterio L,Bianchi G,McBride M,Dominiczak A

    更新日期:2013-08-01 00:00:00

  • Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein.

    abstract::X-linked lissencephaly and "double cortex" are allelic human disorders mapping to Xq22.3-Xq23 associated with arrest of migrating cerebral cortical neurons. We identified a novel 10 kb brain-specific cDNA interrupted by a balanced translocation in an XLIS patient that encodes a novel 40 kDa predicted protein named Dou...


    pub_type: 杂志文章


    authors: Gleeson JG,Allen KM,Fox JW,Lamperti ED,Berkovic S,Scheffer I,Cooper EC,Dobyns WB,Minnerath SR,Ross ME,Walsh CA

    更新日期:1998-01-09 00:00:00

  • Maternal-fetal immune tolerance, block by block.

    abstract::How difficult is to go from egg to implanted embryo? The evolution of placentation in eutherian mammals created enormous challenges, in particular to the maternal immune system, as the fetus expresses paternal antigens that are capable of triggering immune rejection. Samstein et al. reveal a role for inducible regulat...


    pub_type: 评论,杂志文章


    authors: Gobert M,Lafaille JJ

    更新日期:2012-07-06 00:00:00

  • Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus.

    abstract::The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reserv...


    pub_type: 杂志文章


    authors: Andersen KG,Shapiro BJ,Matranga CB,Sealfon R,Lin AE,Moses LM,Folarin OA,Goba A,Odia I,Ehiane PE,Momoh M,England EM,Winnicki S,Branco LM,Gire SK,Phelan E,Tariyal R,Tewhey R,Omoniwa O,Fullah M,Fonnie R,Fonnie M,

    更新日期:2015-08-13 00:00:00

  • Scrapie prion protein contains a phosphatidylinositol glycolipid.

    abstract::The scrapie (PrPSc) and cellular (PrPC) prion proteins are encoded by the same gene, and their different properties are thought to arise from posttranslational modifications. We have found a phosphatidylinositol glycolipid on both PrPC and PrP 27-30 (derived from PrPSc by limited proteolysis at the amino terminus). Et...


    pub_type: 杂志文章


    authors: Stahl N,Borchelt DR,Hsiao K,Prusiner SB

    更新日期:1987-10-23 00:00:00