Modulation of RNA polymerase assembly dynamics in transcriptional regulation.

Abstract:

:The interaction of transcription factors with target genes is highly dynamic. Whether the dynamic nature of these interactions is merely an intrinsic property of transcription factors or serves a regulatory role is unknown. Here we have used single-cell fluorescence imaging combined with computational modeling and chromatin immunoprecipitation to analyze transcription complex dynamics in gene regulation during the cell cycle in living cells. We demonstrate a link between the dynamics of RNA polymerase I (RNA Pol I) assembly and transcriptional output. We show that transcriptional upregulation is accompanied by prolonged retention of RNA Pol I components at the promoter, resulting in longer promoter dwell time, and an increase in the steady-state population of assembling polymerase. As a consequence, polymerase assembly efficiency and, ultimately, the rate of entry into processive elongation are elevated. Our results show that regulation of rDNA transcription in vivo occurs via modulation of the efficiency of transcription complex subunit capture and assembly.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Gorski SA,Snyder SK,John S,Grummt I,Misteli T

doi

10.1016/j.molcel.2008.04.021

subject

Has Abstract

pub_date

2008-05-23 00:00:00

pages

486-97

issue

4

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(08)00323-7

journal_volume

30

pub_type

杂志文章
  • Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity.

    abstract::Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue lo...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.11.013

    authors: Chen C,Ha BH,Thévenin AF,Lou HJ,Zhang R,Yip KY,Peterson JR,Gerstein M,Kim PM,Filippakopoulos P,Knapp S,Boggon TJ,Turk BE

    更新日期:2014-01-09 00:00:00

  • Engineering biological systems with synthetic RNA molecules.

    abstract::RNA molecules play diverse functional roles in natural biological systems. There has been growing interest in designing synthetic RNA counterparts for programming biological function. The design of synthetic RNA molecules that exhibit diverse activities, including sensing, regulatory, information processing, and scaff...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2011.08.023

    authors: Liang JC,Bloom RJ,Smolke CD

    更新日期:2011-09-16 00:00:00

  • CENP-A targeting moves a step back.

    abstract::In a recent issue of Molecular Cell, Pidoux et al. (2009) and Williams et al. (2009) identify S. pombe Scm3 as the proximate factor in the Cnp1/CENP-A deposition pathway, providing a direct connection to centromere-localized Mis16-Mis18. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2009.02.006

    authors: Baker RE

    更新日期:2009-02-27 00:00:00

  • Ribosomal Proteins Regulate MHC Class I Peptide Generation for Immunosurveillance.

    abstract::The MHC class I antigen presentation system enables T cell immunosurveillance of cancers and viruses. A substantial fraction of the immunopeptidome derives from rapidly degraded nascent polypeptides (DRiPs). By knocking down each of the 80 ribosomal proteins, we identified proteins that modulate peptide generation wit...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2018.12.020

    authors: Wei J,Kishton RJ,Angel M,Conn CS,Dalla-Venezia N,Marcel V,Vincent A,Catez F,Ferré S,Ayadi L,Marchand V,Dersh D,Gibbs JS,Ivanov IP,Fridlyand N,Couté Y,Diaz JJ,Qian SB,Staudt LM,Restifo NP,Yewdell JW

    更新日期:2019-03-21 00:00:00

  • Structural basis of Rho GTPase-mediated activation of the formin mDia1.

    abstract::Diaphanous-related formins (DRFs) regulate dynamics of unbranched actin filaments during cell contraction and cytokinesis. DRFs are autoinhibited through intramolecular binding of a Diaphanous autoinhibitory domain (DAD) to a conserved N-terminal regulatory element. Autoinhibition is relieved through binding of the GT...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.04.002

    authors: Otomo T,Otomo C,Tomchick DR,Machius M,Rosen MK

    更新日期:2005-04-29 00:00:00

  • Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC.

    abstract::Gene expression mediated by viral vectors is subject to cell-to-cell variability, which limits the accuracy of gene delivery. When coupled with single-cell measurements, however, such variability provides an efficient means to quantify signaling dynamics in mammalian cells. Here, we illustrate the utility of this appr...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.01.014

    authors: Wong JV,Yao G,Nevins JR,You L

    更新日期:2011-02-04 00:00:00

  • Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in RPN13 and INO80G.

    abstract::Deubiquitinating enzymes (DUBs) control vital processes in eukaryotes by hydrolyzing ubiquitin adducts. Their activities are tightly regulated, but the mechanisms remain elusive. In particular, the DUB UCH-L5 can be either activated or inhibited by conserved regulatory proteins RPN13 and INO80G, respectively. Here we ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.12.039

    authors: Sahtoe DD,van Dijk WJ,El Oualid F,Ekkebus R,Ovaa H,Sixma TK

    更新日期:2015-03-05 00:00:00

  • Bax exists in a dynamic equilibrium between the cytosol and mitochondria to control apoptotic priming.

    abstract::The proapoptotic Bcl-2 protein Bax is predominantly found in the cytosol of nonapoptotic cells and is commonly thought to translocate to mitochondria following an apoptotic stimulus. The current model for Bax activation is that BH3 proteins bind to cytosolic Bax, initiating mitochondrial targeting and outer-membrane p...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.12.022

    authors: Schellenberg B,Wang P,Keeble JA,Rodriguez-Enriquez R,Walker S,Owens TW,Foster F,Tanianis-Hughes J,Brennan K,Streuli CH,Gilmore AP

    更新日期:2013-03-07 00:00:00

  • The pathway for DNA recognition and RNA integration by a group II intron retrotransposon.

    abstract::Group II intron RNPs are mobile genetic elements that attack and invade duplex DNA. In this work, we monitor the invasion reaction in vitro and establish a quantitative kinetic framework for the steps of this complex cascade. We find that target site specificity is achieved after DNA binding, which occurs nonspecifica...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00069-8

    authors: Aizawa Y,Xiang Q,Lambowitz AM,Pyle AM

    更新日期:2003-03-01 00:00:00

  • Cyclic di-GMP in Streptomycetes: A New Conformation, New Binding Mode, New Receptor, and a New Mechanism to Control Cell Development.

    abstract::A recent paper by Gallagher et al. (2020) demonstrates that c-di-GMP controls spore formation in Streptomyces venezuelae through sequestering the sporulation sigma factor σWhiG and presents the crystal structure of a ternary complex between c-di-GMP, σWhiG, and its anti-sigma factor, RsiG. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2020.01.018

    authors: Chou SH,Galperin MY

    更新日期:2020-02-06 00:00:00

  • Topography for independent binding of alpha-helical and PPII-helical ligands to a peroxisomal SH3 domain.

    abstract::While the function of most small signaling domains is confined to binary ligand interactions, the peroxisomal Pex13p SH3 domain has the unique capacity of binding to two different ligands, Pex5p and Pex14p. We have used this domain as a model to decipher its structurally independent ligand binding sites. By the combin...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00749-9

    authors: Douangamath A,Filipp FV,Klein AT,Barnett P,Zou P,Voorn-Brouwer T,Vega MC,Mayans OM,Sattler M,Distel B,Wilmanns M

    更新日期:2002-11-01 00:00:00

  • Structure and dynamics of the mammalian ribosomal pretranslocation complex.

    abstract::Although the structural core of the ribosome is conserved in all kingdoms of life, eukaryotic ribosomes are significantly larger and more complex than their bacterial counterparts. The extent to which these differences influence the molecular mechanism of translation remains elusive. Multiparticle cryo-electron micros...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.07.040

    authors: Budkevich T,Giesebrecht J,Altman RB,Munro JB,Mielke T,Nierhaus KH,Blanchard SC,Spahn CM

    更新日期:2011-10-21 00:00:00

  • Uncoupling of sister replisomes during eukaryotic DNA replication.

    abstract::The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes. Some data imply that ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2010.11.027

    authors: Yardimci H,Loveland AB,Habuchi S,van Oijen AM,Walter JC

    更新日期:2010-12-10 00:00:00

  • Multidomain Convergence of Argonaute during RISC Assembly Correlates with the Formation of Internal Water Clusters.

    abstract::Despite the relevance of Argonaute proteins in RNA silencing, little is known about the structural steps of small RNA loading to form RNA-induced silencing complexes (RISCs). We report the 1.9 Å crystal structure of human Argonaute4 with guide RNA. Comparison with the previously determined apo structure of Neurospora ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2019.06.011

    authors: Park MS,Araya-Secchi R,Brackbill JA,Phan HD,Kehling AC,Abd El-Wahab EW,Dayeh DM,Sotomayor M,Nakanishi K

    更新日期:2019-08-22 00:00:00

  • Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.

    abstract::Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2. lgg-1 is essential for degradation of p...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2015.11.019

    authors: Wu F,Watanabe Y,Guo XY,Qi X,Wang P,Zhao HY,Wang Z,Fujioka Y,Zhang H,Ren JQ,Fang TC,Shen YX,Feng W,Hu JJ,Noda NN,Zhang H

    更新日期:2015-12-17 00:00:00

  • Essential role of ERK dimers in the activation of cytoplasmic but not nuclear substrates by ERK-scaffold complexes.

    abstract::Signals transmitted by ERK MAP kinases regulate the functions of multiple substrates present in the nucleus and in the cytoplasm. ERK signals are optimized by scaffold proteins that modulate their intensity and spatial fidelity. Once phosphorylated, ERKs dimerize, but how dimerization impacts on the activation of the ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.07.024

    authors: Casar B,Pinto A,Crespo P

    更新日期:2008-09-05 00:00:00

  • Properties of Stress Granule and P-Body Proteomes.

    abstract::Stress granules and P-bodies are cytosolic biomolecular condensates that dynamically form by the phase separation of RNAs and proteins. They participate in translational control and buffer the proteome. Upon stress, global translation halts and mRNAs bound to the translational machinery and other proteins coalesce to ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2019.09.014

    authors: Youn JY,Dyakov BJA,Zhang J,Knight JDR,Vernon RM,Forman-Kay JD,Gingras AC

    更新日期:2019-10-17 00:00:00

  • Too sweet for autophagy: hexokinase inhibition of mTORC1 activates autophagy.

    abstract::In this issue, Roberts et al. (2014) describe how hexokinase and mTORC1 cooperate to sense disequilibrium between glucose uptake and utilization and direct the balance of anabolism and catabolism to ensure the appropriate use of cellular resources. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2014.02.009

    authors: Kundu M

    更新日期:2014-02-20 00:00:00

  • A branched pathway governing the activation of a developmental transcription factor by regulated intramembrane proteolysis.

    abstract::The proteolytic activation of the membrane-associated transcription factor pro-sigma(K) is controlled by a signal transduction pathway during sporulation in the bacterium Bacillus subtilis. The pro-sigma(K) processing enzyme SpoIVFB, a membrane-embedded metalloprotease, is held inactive by two other integral-membrane ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.05.019

    authors: Campo N,Rudner DZ

    更新日期:2006-07-07 00:00:00

  • Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases.

    abstract::Two cyclin-dependent kinases have been identified in yeast and mammalian RNA polymerase II transcription initiation complexes. We find that the two yeast kinases are indistinguishable in their ability to phosphorylate the RNA polymerase II CTD, and yet in living cells one kinase is a positive regulator and the other a...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80112-4

    authors: Hengartner CJ,Myer VE,Liao SM,Wilson CJ,Koh SS,Young RA

    更新日期:1998-07-01 00:00:00

  • Arginine/serine-rich domains of SR proteins can function as activators of pre-mRNA splicing.

    abstract::Serine/arginine (SR)-rich splicing factors contain an RNA binding domain and an arginine/serine (RS)-rich domain required for protein-protein interactions. In addition to their roles in the basic splicing reaction, SR proteins function as components of splicing enhancer complexes. Here, we investigate the role of RS d...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80076-3

    authors: Graveley BR,Maniatis T

    更新日期:1998-04-01 00:00:00

  • A Tunable Brake for HECT Ubiquitin Ligases.

    abstract::The HECT E3 ligases ubiquitinate numerous transcription factors and signaling molecules, and their activity must be tightly controlled to prevent cancer, immune disorders, and other diseases. In this study, we have found unexpectedly that peptide linkers tethering WW domains in several HECT family members are key regu...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2017.03.020

    authors: Chen Z,Jiang H,Xu W,Li X,Dempsey DR,Zhang X,Devreotes P,Wolberger C,Amzel LM,Gabelli SB,Cole PA

    更新日期:2017-05-04 00:00:00

  • CRD-BP protects the coding region of betaTrCP1 mRNA from miR-183-mediated degradation.

    abstract::miRNAs are largely known to base pair with the 3'UTR of target mRNAs, downregulating their stability and translation. mRNA of betaTrCP1 ubiquitin ligase is very unstable, but unlike the majority of mRNAs where 3'UTR determines the rate of mRNA turnover, betaTrCP1 mRNA contains cis-acting destabilizing elements within ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.06.007

    authors: Elcheva I,Goswami S,Noubissi FK,Spiegelman VS

    更新日期:2009-07-31 00:00:00

  • Late S phase-specific recruitment of Mre11 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae.

    abstract::In Saccharomyces cerevisiae, telomere replication occurs in late S phase and is accompanied by dynamic remodeling of its protein components. Here, we show that MRX (Mre11-Rad50-Xrs2), an evolutionarily conserved protein complex involved in DNA double-strand break (DSB) repair, is recruited to the telomeres in late S p...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2005.01.014

    authors: Takata H,Tanaka Y,Matsuura A

    更新日期:2005-02-18 00:00:00

  • Signaling from across the way: transactivation of VEGF receptors by HSPGs.

    abstract::Heparan sulfate proteoglycans (HSPGs) influence the signaling of many growth factors, and recent work shows that they can promote VEGF signaling in trans from the surface of an adjacent cell. This mode of signaling also alters the activation state and internalization of VEGF receptors. ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2006.05.004

    authors: Selleck SB

    更新日期:2006-05-19 00:00:00

  • Acetylation Enhances TET2 Function in Protecting against Abnormal DNA Methylation during Oxidative Stress.

    abstract::TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.12.013

    authors: Zhang YW,Wang Z,Xie W,Cai Y,Xia L,Easwaran H,Luo J,Yen RC,Li Y,Baylin SB

    更新日期:2017-01-19 00:00:00

  • Structure and Function in Drosophila Chromosomes: Visualizing Topological Domains.

    abstract::Cardozo Gizzi et al. (2019) develop a new sequential imaging methodology (Hi-M) for observing chromosome structure in the Drosophila blastoderm and find that topological domains in single nuclei change in response to transcriptional activation. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2019.03.017

    authors: Larson DR

    更新日期:2019-04-04 00:00:00

  • Frozen in Transcription: Cryo-EM Structures of Pol II Transcribing through a Nucleosome.

    abstract::In a recent publication in Science, Kujirai et al. (2018) use single-particle cryo-EM to resolve several Pol II-nucleosome interactions, shedding new light on transcription elongation in a native chromatin environment. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2018.11.027

    authors: Noe Gonzalez M,Conaway RC,Conaway JW

    更新日期:2018-12-06 00:00:00

  • A Rapid Induction Mechanism for Lin28a in Trophic Responses.

    abstract::Environmental cues provoke rapid transitions in gene expression to support growth and cellular plasticity through incompletely understood mechanisms. Lin28 RNA-binding proteins have evolutionarily conserved roles in post-transcriptional coordination of pro-growth gene expression, but signaling pathways allowing trophi...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.12.025

    authors: Amen AM,Ruiz-Garzon CR,Shi J,Subramanian M,Pham DL,Meffert MK

    更新日期:2017-02-02 00:00:00

  • The tangled circuitry of metabolism and apoptosis.

    abstract::For single-cell organisms, nutrient uptake and metabolism are central to the fundamental decision of whether to grow or divide. In metazoans, cell fate decisions are more complex: organismal homeostasis must be strictly maintained by balancing cell proliferation and death. Despite this increased complexity, cell fate ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2012.12.026

    authors: Andersen JL,Kornbluth S

    更新日期:2013-02-07 00:00:00