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












  • Identification of a Tissue-Restricted Isoform of SIRT1 Defines a Regulatory Domain that Encodes Specificity.

    abstract::The conserved NAD+-dependent deacylase SIRT1 plays pivotal, sometimes contrasting, roles in diverse physiological and pathophysiological conditions. In this study, we uncover a tissue-restricted isoform of SIRT1 (SIRT1-ΔE2) that lacks exon 2 (E2). Candidate-based screening of SIRT1 substrates demonstrated that the dom...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Deota S,Chattopadhyay T,Ramachandran D,Armstrong E,Camacho B,Maniyadath B,Fulzele A,Gonzalez-de-Peredo A,Denu JM,Kolthur-Seetharam U

    更新日期:2017-03-28 00:00:00

  • Rational Reprogramming of Cellular States by Combinatorial Perturbation.

    abstract::Ectopic expression of transcription factors (TFs) can reprogram cell state. However, because of the large combinatorial space of possible TF cocktails, it remains difficult to identify TFs that reprogram specific cell types. Here, we develop Reprogram-Seq to experimentally screen thousands of TF cocktails for reprogra...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Duan J,Li B,Bhakta M,Xie S,Zhou P,Munshi NV,Hon GC

    更新日期:2019-06-18 00:00:00

  • Functional Access to Neuron Subclasses in Rodent and Primate Forebrain.

    abstract::Viral vectors enable foreign proteins to be expressed in brains of non-genetic species, including non-human primates. However, viruses targeting specific neuron classes have proved elusive. Here we describe viral promoters and strategies for accessing GABAergic interneurons and their molecularly defined subsets in the...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Mehta P,Kreeger L,Wylie DC,Pattadkal JJ,Lusignan T,Davis MJ,Turi GF,Li WK,Whitmire MP,Chen Y,Kajs BL,Seidemann E,Priebe NJ,Losonczy A,Zemelman BV

    更新日期:2019-03-05 00:00:00

  • Insights into Centromere DNA Bending Revealed by the Cryo-EM Structure of the Core Centromere Binding Factor 3 with Ndc10.

    abstract::The centromere binding factor 3 (CBF3) complex binds the third centromere DNA element in organisms with point centromeres, such as S. cerevisiae. It is an essential complex for assembly of the kinetochore in these organisms, as it facilitates genetic centromere specification and allows association of all other kinetoc...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Zhang W,Lukoyanova N,Miah S,Lucas J,Vaughan CK

    更新日期:2018-07-17 00:00:00

  • Fusion of Reprogramming Factors Alters the Trajectory of Somatic Lineage Conversion.

    abstract::Simultaneous expression of Oct4, Klf4, Sox2, and cMyc induces pluripotency in somatic cells (iPSCs). Replacing Oct4 with the neuro-specific factor Brn4 leads to transdifferentiation of fibroblasts into induced neural stem cells (iNSCs). However, Brn4 was recently found to induce transient acquisition of pluripotency b...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Velychko S,Kang K,Kim SM,Kwak TH,Kim KP,Park C,Hong K,Chung C,Hyun JK,MacCarthy CM,Wu G,Schöler HR,Han DW

    更新日期:2019-04-02 00:00:00

  • Downregulation of a GPCR by β-Arrestin2-Mediated Switch from an Endosomal to a TGN Recycling Pathway.

    abstract::Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in nutrient homeostasis. GIP receptor (GIPR) is constitutively internalized and returned to the plasma membrane, atypical behavior for a G-protein-coupled receptor (GPCR). GIP promotes GIPR downregulation from the plasma membrane by inh...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Abdullah N,Beg M,Soares D,Dittman JS,McGraw TE

    更新日期:2016-12-13 00:00:00

  • Metabolic Control of Gametophore Shoot Formation through Arginine in the Moss Physcomitrium patens.

    abstract::Shoot formation is accompanied by active cell proliferation and expansion, requiring that metabolic state adapts to developmental control. Despite the importance of such metabolic reprogramming, it remains unclear how development and metabolism are integrated. Here, we show that disruption of ANGUSTIFOLIA3 orthologs (...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Kawade K,Horiguchi G,Hirose Y,Oikawa A,Hirai MY,Saito K,Fujita T,Tsukaya H

    更新日期:2020-09-08 00:00:00

  • An Allosteric Interaction Network Promotes Conformation State-Dependent Eviction of the Nas6 Assembly Chaperone from Nascent 26S Proteasomes.

    abstract::The 26S proteasome is the central ATP-dependent protease in eukaryotes and is essential for organismal health. Proteasome assembly is mediated by several dedicated, evolutionarily conserved chaperone proteins. These chaperones associate transiently with assembly intermediates but are absent from mature proteasomes. Ch...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Nemec AA,Peterson AK,Warnock JL,Reed RG,Tomko RJ Jr

    更新日期:2019-01-08 00:00:00

  • Bone Morphogenic Proteins Are Immunoregulatory Cytokines Controlling FOXP3+ Treg Cells.

    abstract::Bone morphogenic proteins (BMPs) are members of the transforming growth factor β (TGF-β) cytokine family promoting differentiation, homeostasis, and self-renewal of multiple tissues. We show that signaling through the bone morphogenic protein receptor 1α (BMPR1α) sustains expression of FOXP3 in Treg cells in periphera...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Browning LM,Miller C,Kuczma M,Pietrzak M,Jing Y,Rempala G,Muranski P,Ignatowicz L,Kraj P

    更新日期:2020-10-06 00:00:00

  • Timed Synaptic Inhibition Shapes NMDA Spikes, Influencing Local Dendritic Processing and Global I/O Properties of Cortical Neurons.

    abstract::The NMDA spike is a long-lasting nonlinear phenomenon initiated locally in the dendritic branches of a variety of cortical neurons. It plays a key role in synaptic plasticity and in single-neuron computations. Combining dynamic system theory and computational approaches, we now explore how the timing of synaptic inhib...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Doron M,Chindemi G,Muller E,Markram H,Segev I

    更新日期:2017-11-07 00:00:00

  • Discovery and Characterization of piRNAs in the Human Fetal Ovary.

    abstract::Piwi-interacting RNAs (piRNAs), a class of 26- to 32-nt non-coding RNAs (ncRNAs), function in germline development, transposon silencing, and epigenetic regulation. We performed deep sequencing and annotation of untreated and periodate-treated small RNA cDNA libraries from human fetal and adult germline and reference ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Williams Z,Morozov P,Mihailovic A,Lin C,Puvvula PK,Juranek S,Rosenwaks Z,Tuschl T

    更新日期:2015-10-27 00:00:00

  • Synapsin III acts downstream of semaphorin 3A/CDK5 signaling to regulate radial migration and orientation of pyramidal neurons in vivo.

    abstract::Synapsin III (SynIII) is a phosphoprotein that is highly expressed at early stages of neuronal development. Whereas in vitro evidence suggests a role for SynIII in neuronal differentiation, in vivo evidence is lacking. Here, we demonstrate that in vivo downregulation of SynIII expression affects neuronal migration and...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Perlini LE,Szczurkowska J,Ballif BA,Piccini A,Sacchetti S,Giovedì S,Benfenati F,Cancedda L

    更新日期:2015-04-14 00:00:00

  • Dual and Direction-Selective Mechanisms of Phosphate Transport by the Vesicular Glutamate Transporter.

    abstract::Vesicular glutamate transporters (VGLUTs) fill synaptic vesicles with glutamate and are thus essential for glutamatergic neurotransmission. However, VGLUTs were originally discovered as members of a transporter subfamily specific for inorganic phosphate (Pi). It is still unclear how VGLUTs accommodate glutamate transp...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Preobraschenski J,Cheret C,Ganzella M,Zander JF,Richter K,Schenck S,Jahn R,Ahnert-Hilger G

    更新日期:2018-04-10 00:00:00

  • Single-Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis.

    abstract::Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Henriques F,Bedard AH,Guilherme A,Kelly M,Chi J,Zhang P,Lifshitz LM,Bellvé K,Rowland LA,Yenilmez B,Kumar S,Wang Y,Luban J,Weinstein LS,Lin JD,Cohen P,Czech MP

    更新日期:2020-08-04 00:00:00

  • TCF1 and LEF1 Control Treg Competitive Survival and Tfr Development to Prevent Autoimmune Diseases.

    abstract::CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient exp...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Yang BH,Wang K,Wan S,Liang Y,Yuan X,Dong Y,Cho S,Xu W,Jepsen K,Feng GS,Lu LF,Xue HH,Fu W

    更新日期:2019-06-18 00:00:00

  • Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development.

    abstract::We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration and long-duration spaceflight. Previous studies have identified miRNAs that regulate rodent responses to spaceflight in low-Earth orbit, and we have confirm...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Malkani S,Chin CR,Cekanaviciute E,Mortreux M,Okinula H,Tarbier M,Schreurs AS,Shirazi-Fard Y,Tahimic CGT,Rodriguez DN,Sexton BS,Butler D,Verma A,Bezdan D,Durmaz C,MacKay M,Melnick A,Meydan C,Li S,Garrett-Bakelman F,

    更新日期:2020-12-08 00:00:00

  • A Single Templating RNA in Yeast Telomerase.

    abstract::The number of essential telomerase components in the active ribonucleoprotein (RNP) has important implications for its mechanism of action yet is by and large unknown. We report that two differentially tagged TLC1 RNAs endogenously expressed in a heterozygous diploid and simultaneously detected via multi-color fluores...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Bajon E,Laterreur N,Wellinger RJ

    更新日期:2015-07-21 00:00:00

  • Culling Less Fit Neurons Protects against Amyloid-β-Induced Brain Damage and Cognitive and Motor Decline.

    abstract::Alzheimer's disease (AD) is the most common form of dementia, impairing cognitive and motor functions. One of the pathological hallmarks of AD is neuronal loss, which is not reflected in mouse models of AD. Therefore, the role of neuronal death is still uncertain. Here, we used a Drosophila AD model expressing a secre...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Coelho DS,Schwartz S,Merino MM,Hauert B,Topfel B,Tieche C,Rhiner C,Moreno E

    更新日期:2018-12-26 00:00:00

  • SNAREs Controlling Vesicular Release of BDNF and Development of Callosal Axons.

    abstract::At presynaptic active zones, exocytosis of neurotransmitter vesicles (SVs) is driven by SNARE complexes that recruit Syb2 and SNAP25. However, it remains unknown which SNAREs promote the secretion of neuronal proteins, including those essential for circuit development and experience-dependent plasticity. Here we demon...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Shimojo M,Courchet J,Pieraut S,Torabi-Rander N,Sando R 3rd,Polleux F,Maximov A

    更新日期:2015-05-19 00:00:00

  • Membrane-sculpting BAR domains generate stable lipid microdomains.

    abstract::Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of many cellular processes involving membrane dynamics. BAR domains sculpt phosphoinositide-rich membranes to generate membrane protrusions or invaginations. Here, we report that, in addition to regulating membrane geometry, BAR domains can generate extr...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Zhao H,Michelot A,Koskela EV,Tkach V,Stamou D,Drubin DG,Lappalainen P

    更新日期:2013-09-26 00:00:00

  • Antibiotics Disrupt Coordination between Transcriptional and Phenotypic Stress Responses in Pathogenic Bacteria.

    abstract::Bacterial genes that change in expression upon environmental disturbance have commonly been seen as those that must also phenotypically matter. However, several studies suggest that differentially expressed genes are rarely phenotypically important. We demonstrate, for Gram-positive and Gram-negative bacteria, that th...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Jensen PA,Zhu Z,van Opijnen T

    更新日期:2017-08-15 00:00:00

  • Loss of Caveolin-1 in Metastasis-Associated Macrophages Drives Lung Metastatic Growth through Increased Angiogenesis.

    abstract::Although it is well established that tumor-associated macrophages take part in each step of cancer progression, less is known about the distinct role of the so-called metastasis-associated macrophages (MAMs) at the metastatic site. Previous studies reported that Caveolin-1 (Cav1) has both tumor-promoting and tumor-sup...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Celus W,Di Conza G,Oliveira AI,Ehling M,Costa BM,Wenes M,Mazzone M

    更新日期:2017-12-05 00:00:00

  • Raptor-Mediated Proteasomal Degradation of Deamidated 4E-BP2 Regulates Postnatal Neuronal Translation and NF-κB Activity.

    abstract::The translation initiation repressor 4E-BP2 is deamidated in the brain on asparagines N99/N102 during early postnatal brain development. This post-translational modification enhances 4E-BP2 association with Raptor, a central component of mTORC1 and alters the kinetics of excitatory synaptic transmission. We show that ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Kouloulia S,Hallin EI,Simbriger K,Amorim IS,Lach G,Amvrosiadis T,Chalkiadaki K,Kampaite A,Truong VT,Hooshmandi M,Jafarnejad SM,Skehel P,Kursula P,Khoutorsky A,Gkogkas CG

    更新日期:2019-12-10 00:00:00

  • Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.

    abstract::Hox genes are required for the development of the intestinal cecum, a major organ of plant-eating species. We have analyzed the transcriptional regulation of Hoxd genes in cecal buds and show that they are controlled by a series of enhancers located in a gene desert flanking the HoxD cluster. The start site of two opp...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Delpretti S,Montavon T,Leleu M,Joye E,Tzika A,Milinkovitch M,Duboule D

    更新日期:2013-10-17 00:00:00

  • Control of embryonic stem cell identity by BRD4-dependent transcriptional elongation of super-enhancer-associated pluripotency genes.

    abstract::Transcription factors and chromatin-remodeling complexes are key determinants of embryonic stem cell (ESC) identity. Here, we demonstrate that BRD4, a member of the bromodomain and extraterminal domain (BET) family of epigenetic readers, regulates the self-renewal ability and pluripotency of ESCs. BRD4 inhibition resu...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Di Micco R,Fontanals-Cirera B,Low V,Ntziachristos P,Yuen SK,Lovell CD,Dolgalev I,Yonekubo Y,Zhang G,Rusinova E,Gerona-Navarro G,Cañamero M,Ohlmeyer M,Aifantis I,Zhou MM,Tsirigos A,Hernando E

    更新日期:2014-10-09 00:00:00

  • Interactome of two diverse RNA granules links mRNA localization to translational repression in neurons.

    abstract::Transport of RNAs to dendrites occurs in neuronal RNA granules, which allows local synthesis of specific proteins at active synapses on demand, thereby contributing to learning and memory. To gain insight into the machinery controlling dendritic mRNA localization and translation, we established a stringent protocol to...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Fritzsche R,Karra D,Bennett KL,Ang FY,Heraud-Farlow JE,Tolino M,Doyle M,Bauer KE,Thomas S,Planyavsky M,Arn E,Bakosova A,Jungwirth K,Hörmann A,Palfi Z,Sandholzer J,Schwarz M,Macchi P,Colinge J,Superti-Furga G,Kiebl

    更新日期:2013-12-26 00:00:00

  • Cell-Cycle-Regulated Interaction between Mcm10 and Double Hexameric Mcm2-7 Is Required for Helicase Splitting and Activation during S Phase.

    abstract::Mcm2-7 helicase is loaded onto double-stranded origin DNA as an inactive double hexamer (DH) in G1 phase. The mechanisms of Mcm2-7 remodeling that trigger helicase activation in S phase remain unknown. Here, we develop an approach to detect and purify the endogenous DHs directly. Through cellular fractionation, we pro...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Quan Y,Xia Y,Liu L,Cui J,Li Z,Cao Q,Chen XS,Campbell JL,Lou H

    更新日期:2015-12-22 00:00:00

  • Postsynaptic and Presynaptic NMDARs Have Distinct Roles in Visual Circuit Development.

    abstract::To study contributions of N-methyl-D-aspartate receptors (NMDARs) in presynaptic and postsynaptic neurons of the developing visual system, we microinject antisense Morpholino oligonucleotide (MO) against GluN1 into one cell of two-cell-stage Xenopus laevis embryos. The resulting bilateral segregation of MO induces pos...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Kesner P,Schohl A,Warren EC,Ma F,Ruthazer ES

    更新日期:2020-07-28 00:00:00

  • Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells.

    abstract::MicroRNA (miRNA) transfer via exosomes may mediate cell-to-cell communication. Interestingly, specific miRNAs are enriched in exosomes in a cell-type-dependent fashion. However, the mechanisms whereby miRNAs are sorted to exosomes and the significance of miRNA transfer to acceptor cells are unclear. We used macrophage...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Squadrito ML,Baer C,Burdet F,Maderna C,Gilfillan GD,Lyle R,Ibberson M,De Palma M

    更新日期:2014-09-11 00:00:00

  • Systematic Kinase Inhibitor Profiling Identifies CDK9 as a Synthetic Lethal Target in NUT Midline Carcinoma.

    abstract::Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) an...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Brägelmann J,Dammert MA,Dietlein F,Heuckmann JM,Choidas A,Böhm S,Richters A,Basu D,Tischler V,Lorenz C,Habenberger P,Fang Z,Ortiz-Cuaran S,Leenders F,Eickhoff J,Koch U,Getlik M,Termathe M,Sallouh M,Greff Z,Varga Z

    更新日期:2017-09-19 00:00:00