Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity.


:Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly. This effect can be recapitulated by partial, adult-restricted inhibition, with both enterocytes and stem cells of the adult midgut emerging as important cell types. In stem cells, Pol I appears to act in the same longevity pathway as Pol III, implicating rRNA synthesis in these cells as the key lifespan determinant. Importantly, reduction in Pol I activity delays broad, age-related impairment and pathology, improving the function of diverse organ systems. Hence, our study shows that Pol I activity in the adult drives systemic, age-related decline in animal health and anticipates mortality.


Cell Rep


Cell reports


Martínez Corrales G,Filer D,Wenz KC,Rogan A,Phillips G,Li M,Feseha Y,Broughton SJ,Alic N




Has Abstract


2020-02-11 00:00:00












  • Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats.

    abstract::Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 m...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Melas PA,Qvist JS,Deidda M,Upreti C,Wei YB,Sanna F,Fratta W,Scherma M,Fadda P,Kandel DB,Kandel ER

    更新日期:2018-03-13 00:00:00

  • Poly(ADP-Ribose) Links the DNA Damage Response and Biomineralization.

    abstract::Biomineralization of the extracellular matrix is an essential, regulated process. Inappropriate mineralization of bone and the vasculature has devastating effects on patient health, yet an integrated understanding of the chemical and cell biological processes that lead to mineral nucleation remains elusive. Here, we r...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Müller KH,Hayward R,Rajan R,Whitehead M,Cobb AM,Ahmad S,Sun M,Goldberga I,Li R,Bashtanova U,Puszkarska AM,Reid DG,Brooks RA,Skepper JN,Bordoloi J,Chow WY,Oschkinat H,Groombridge A,Scherman OA,Harrison JA,Verhulst

    更新日期:2019-06-11 00:00:00

  • The Self-Inactivating KamiCas9 System for the Editing of CNS Disease Genes.

    abstract::Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expre...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Merienne N,Vachey G,de Longprez L,Meunier C,Zimmer V,Perriard G,Canales M,Mathias A,Herrgott L,Beltraminelli T,Maulet A,Dequesne T,Pythoud C,Rey M,Pellerin L,Brouillet E,Perrier AL,du Pasquier R,Déglon N

    更新日期:2017-09-19 00:00:00

  • RNASEK Is a V-ATPase-Associated Factor Required for Endocytosis and the Replication of Rhinovirus, Influenza A Virus, and Dengue Virus.

    abstract::Human rhinovirus (HRV) causes upper respiratory infections and asthma exacerbations. We screened multiple orthologous RNAi reagents and identified host proteins that modulate HRV replication. Here, we show that RNASEK, a transmembrane protein, was needed for the replication of HRV, influenza A virus, and dengue virus....

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Perreira JM,Aker AM,Savidis G,Chin CR,McDougall WM,Portmann JM,Meraner P,Smith MC,Rahman M,Baker RE,Gauthier A,Franti M,Brass AL

    更新日期:2015-08-04 00:00:00

  • Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone.

    abstract::Neurogenesis continues in the ventricular-subventricular zone (V-SVZ) of the adult forebrain from quiescent neural stem cells (NSCs). V-SVZ NSCs are a reservoir for new olfactory bulb (OB) neurons that migrate through the rostral migratory stream (RMS). To generate neurons, V-SVZ NSCs need to activate and enter the ce...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Engler A,Rolando C,Giachino C,Saotome I,Erni A,Brien C,Zhang R,Zimber-Strobl U,Radtke F,Artavanis-Tsakonas S,Louvi A,Taylor V

    更新日期:2018-01-23 00:00:00

  • Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior.

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Miller OH,Bruns A,Ben Ammar I,Mueggler T,Hall BJ

    更新日期:2017-08-22 00:00:00

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Zampieri M,Zimmermann M,Claassen M,Sauer U

    更新日期:2017-05-09 00:00:00

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Barres R,Kirchner H,Rasmussen M,Yan J,Kantor FR,Krook A,Näslund E,Zierath JR

    更新日期:2013-04-25 00:00:00

  • Detecting Microbial Dysbiosis Associated with Pediatric Crohn Disease Despite the High Variability of the Gut Microbiota.

    abstract::The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacteri...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Wang F,Kaplan JL,Gold BD,Bhasin MK,Ward NL,Kellermayer R,Kirschner BS,Heyman MB,Dowd SE,Cox SB,Dogan H,Steven B,Ferry GD,Cohen SA,Baldassano RN,Moran CJ,Garnett EA,Drake L,Otu HH,Mirny LA,Libermann TA,Winter HS

    更新日期:2016-02-02 00:00:00

  • ATP Citrate Lyase Regulates Myofiber Differentiation and Increases Regeneration by Altering Histone Acetylation.

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Das S,Morvan F,Morozzi G,Jourde B,Minetti GC,Kahle P,Rivet H,Brebbia P,Toussaint G,Glass DJ,Fornaro M

    更新日期:2017-12-12 00:00:00

  • Metalloprotease-Dependent Attenuation of BMP Signaling Restricts Cardiac Neural Crest Cell Fate.

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Arai HN,Sato F,Yamamoto T,Woltjen K,Kiyonari H,Yoshimoto Y,Shukunami C,Akiyama H,Kist R,Sehara-Fujisawa A

    更新日期:2019-10-15 00:00:00

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Tischbirek CH,Noda T,Tohmi M,Birkner A,Nelken I,Konnerth A

    更新日期:2019-04-30 00:00:00

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Shin J,He M,Liu Y,Paredes S,Villanova L,Brown K,Qiu X,Nabavi N,Mohrin M,Wojnoonski K,Li P,Cheng HL,Murphy AJ,Valenzuela DM,Luo H,Kapahi P,Krauss R,Mostoslavsky R,Yancopoulos GD,Alt FW,Chua KF,Chen D

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    abstract::Inhibition of the ATPase cycle of the HSP90 chaperone promotes ubiquitylation and proteasomal degradation of its client proteins, which include many oncogenic protein kinases. This provides the rationale for HSP90 inhibitors as cancer therapeutics. However, the mechanism by which HSP90 ATPase inhibition triggers ubiqu...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Li Z,Zhou L,Prodromou C,Savic V,Pearl LH

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  • PARTICLE, a Triplex-Forming Long ncRNA, Regulates Locus-Specific Methylation in Response to Low-Dose Irradiation.

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: O'Leary VB,Ovsepian SV,Carrascosa LG,Buske FA,Radulovic V,Niyazi M,Moertl S,Trau M,Atkinson MJ,Anastasov N

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  • BLM Potentiates c-Jun Degradation and Alters Its Function as an Oncogenic Transcription Factor.

    abstract::Mutations in BLM helicase predispose Bloom syndrome (BS) patients to a wide spectrum of cancers. We demonstrate that MIB1-ubiquitylated BLM in G1 phase functions as an adaptor protein by enhancing the binding of transcription factor c-Jun and its E3 ligase, Fbw7α. BLM enhances the K48/K63-linked ubiquitylation on c-Ju...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Priyadarshini R,Hussain M,Attri P,Kaur E,Tripathi V,Priya S,Dhapola P,Saha D,Madhavan V,Chowdhury S,Sengupta S

    更新日期:2018-07-24 00:00:00

  • p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network.

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Marshall CB,Mays DJ,Beeler JS,Rosenbluth JM,Boyd KL,Santos Guasch GL,Shaver TM,Tang LJ,Liu Q,Shyr Y,Venters BJ,Magnuson MA,Pietenpol JA

    更新日期:2016-03-15 00:00:00

  • Terminal Nerve GnRH3 Neurons Mediate Slow Avoidance of Carbon Dioxide in Larval Zebrafish.

    abstract::Escape responses to threatening stimuli are vital for survival in all animal species. Larval zebrafish display fast escape responses when exposed to tactile, acoustic, and visual stimuli. However, their behavioral responses to chemosensory stimuli remain unknown. In this study, we found that carbon dioxide (CO2) induc...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Koide T,Yabuki Y,Yoshihara Y

    更新日期:2018-01-30 00:00:00

  • HUWE1 ubiquitylates and degrades the RAC activator TIAM1 promoting cell-cell adhesion disassembly, migration, and invasion.

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Vaughan L,Tan CT,Chapman A,Nonaka D,Mack NA,Smith D,Booton R,Hurlstone AF,Malliri A

    更新日期:2015-01-06 00:00:00

  • VEGF-A from Granuloma Macrophages Regulates Granulomatous Inflammation by a Non-angiogenic Pathway during Mycobacterial Infection.

    abstract::Many autoimmune and infectious diseases are characterized by the formation of granulomas which are inflammatory lesions that consist of spatially organized immune cells. These sites protect the host and control pathogens like Mycobacterium tuberculosis (Mtb), but are highly inflammatory and cause pathology. Using baci...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Harding JS,Herbath M,Chen Y,Rayasam A,Ritter A,Csoka B,Hasko G,Michael IP,Fabry Z,Nagy A,Sandor M

    更新日期:2019-05-14 00:00:00

  • Dead Cells Induce Innate Anergy via Mertk after Acute Viral Infection.

    abstract::Infections can result in a temporarily restricted unresponsiveness of the innate immune response, thereby limiting pathogen control. Mechanisms of such unresponsiveness are well studied in lipopolysaccharide tolerance; however, whether mechanisms of tolerance limit innate immunity during virus infection remains unknow...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Adomati T,Cham LB,Hamdan TA,Bhat H,Duhan V,Li F,Ali M,Lang E,Huang A,Naser E,Khairnar V,Friedrich SK,Lang J,Friebus-Kardash J,Bergerhausen M,Schiller M,Machlah YM,Lang F,Häussinger D,Ferencik S,Hardt C,Lang PA,

    更新日期:2020-03-17 00:00:00

  • MERVL/Zscan4 Network Activation Results in Transient Genome-wide DNA Demethylation of mESCs.

    abstract::Mouse embryonic stem cells are dynamic and heterogeneous. For example, rare cells cycle through a state characterized by decondensed chromatin and expression of transcripts, including the Zscan4 cluster and MERVL endogenous retrovirus, which are usually restricted to preimplantation embryos. Here, we further character...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Eckersley-Maslin MA,Svensson V,Krueger C,Stubbs TM,Giehr P,Krueger F,Miragaia RJ,Kyriakopoulos C,Berrens RV,Milagre I,Walter J,Teichmann SA,Reik W

    更新日期:2016-09-27 00:00:00

  • Interplay of Histone Marks with Serine ADP-Ribosylation.

    abstract::Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1). In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response. Here, we s...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Bartlett E,Bonfiglio JJ,Prokhorova E,Colby T,Zobel F,Ahel I,Matic I

    更新日期:2018-09-25 00:00:00

  • Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates.

    abstract::Generating mammalian cells with desired mitochondrial DNA (mtDNA) sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nuclear DNA (nDNA) combinations by transferring iso...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Patananan AN,Sercel AJ,Wu TH,Ahsan FM,Torres A Jr,Kennedy SAL,Vandiver A,Collier AJ,Mehrabi A,Van Lew J,Zakin L,Rodriguez N,Sixto M,Tadros W,Lazar A,Sieling PA,Nguyen TL,Dawson ER,Braas D,Golovato J,Cisneros L,V

    更新日期:2020-12-29 00:00:00

  • Dissecting Cell Lineage Specification and Sex Fate Determination in Gonadal Somatic Cells Using Single-Cell Transcriptomics.

    abstract::Sex determination is a unique process that allows the study of multipotent progenitors and their acquisition of sex-specific fates during differentiation of the gonad into a testis or an ovary. Using time series single-cell RNA sequencing (scRNA-seq) on ovarian Nr5a1-GFP+ somatic cells during sex determination, we ide...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Stévant I,Kühne F,Greenfield A,Chaboissier MC,Dermitzakis ET,Nef S

    更新日期:2019-03-19 00:00:00

  • Antibody Treatment of Ebola and Sudan Virus Infection via a Uniquely Exposed Epitope within the Glycoprotein Receptor-Binding Site.

    abstract::Previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because the RBS is occluded on the viral surface. We report a monoclonal antibody (FVM04) that targets a uniquely exposed epitope within the RBS; cross-neutralizes E...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Howell KA,Qiu X,Brannan JM,Bryan C,Davidson E,Holtsberg FW,Wec AZ,Shulenin S,Biggins JE,Douglas R,Enterlein SG,Turner HL,Pallesen J,Murin CD,He S,Kroeker A,Vu H,Herbert AS,Fusco ML,Nyakatura EK,Lai JR,Keck ZY,

    更新日期:2016-05-17 00:00:00

  • Interplay between Extracellular Matrix Stiffness and JAM-A Regulates Mechanical Load on ZO-1 and Tight Junction Assembly.

    abstract::Tight-junction-regulated actomyosin activity determines epithelial and endothelial tension on adherens junctions and drives morphogenetic processes; however, whether or not tight junctions themselves are under tensile stress is not clear. Here, we use a tension sensor based on ZO-1, a scaffolding protein that links th...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Haas AJ,Zihni C,Ruppel A,Hartmann C,Ebnet K,Tada M,Balda MS,Matter K

    更新日期:2020-07-21 00:00:00

  • Small-Molecule and CRISPR Screening Converge to Reveal Receptor Tyrosine Kinase Dependencies in Pediatric Rhabdoid Tumors.

    abstract::Cancer is often seen as a disease of mutations and chromosomal abnormalities. However, some cancers, including pediatric rhabdoid tumors (RTs), lack recurrent alterations targetable by current drugs and need alternative, informed therapeutic options. To nominate potential targets, we performed a high-throughput small-...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Oberlick EM,Rees MG,Seashore-Ludlow B,Vazquez F,Nelson GM,Dharia NV,Weir BA,Tsherniak A,Ghandi M,Krill-Burger JM,Meyers RM,Wang X,Montgomery P,Root DE,Bieber JM,Radko S,Cheah JH,Hon CS,Shamji AF,Clemons PA,Park PJ

    更新日期:2019-08-27 00:00:00

  • Piwi Is a Key Regulator of Both Somatic and Germline Stem Cells in the Drosophila Testis.

    abstract::The Piwi-piRNA pathway is well known for its germline function, yet its somatic role remains elusive. We show here that Piwi is required autonomously not only for germline stem cell (GSC) but also for somatic cyst stem cell (CySC) maintenance in the Drosophila testis. Reducing Piwi activity in the testis caused defect...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Gonzalez J,Qi H,Liu N,Lin H

    更新日期:2015-07-07 00:00:00

  • Follicular Regulatory T Cells Can Access the Germinal Center Independently of CXCR5.

    abstract::The germinal center (GC) response is critical for generating high-affinity humoral immunity and immunological memory, which forms the basis of successful immunization. Control of the GC response is thought to require follicular regulatory T (Tfr) cells, a subset of suppressive Foxp3+ regulatory T cells located within ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Vanderleyden I,Fra-Bido SC,Innocentin S,Stebegg M,Okkenhaug H,Evans-Bailey N,Pierson W,Denton AE,Linterman MA

    更新日期:2020-01-21 00:00:00