abstract：:DNA methylation directed by 24-nucleotide (nt) small interfering RNAs (siRNAs) plays critical roles in gene regulation and transposon silencing in Arabidopsis. 24-nt siRNAs are known to be processed from double-stranded RNAs by Dicer-like 3 (DCL3) and loaded into the effector Argonaute 4 (AGO4). Here we report a disti...

journal_title：Molecular cell

authors： Ye R,Chen Z,Lian B,Rowley MJ,Xia N,Chai J,Li Y,He XJ,Wierzbicki AT,Qi Y

更新日期：2016-01-21 00:00:00

abstract：:Genome-wide profiling of histone modifications can provide systematic insight into the regulatory elements and programs engaged in a given cell type. However, conventional chromatin immunoprecipitation and sequencing (ChIP-seq) does not capture quantitative information on histone modification levels, requires large am...

journal_title：Molecular cell

authors： van Galen P,Viny AD,Ram O,Ryan RJ,Cotton MJ,Donohue L,Sievers C,Drier Y,Liau BB,Gillespie SM,Carroll KM,Cross MB,Levine RL,Bernstein BE

更新日期：2016-01-07 00:00:00

abstract：:Protein synthesis is a major target within the bacterial cell for antibiotics. Investigations into ribosome-targeting antibiotics have provided much needed functional and structural insight into their mechanism of action. However, the increasing prevalence of multi-drug-resistant bacteria has limited the utility of ou...

journal_title：Molecular cell

authors： Arenz S,Wilson DN

更新日期：2016-01-07 00:00:00

abstract：:The transition from transcription initiation to elongation at promoters of primary response genes (PRGs) in metazoan cells is controlled by inducible transcription factors, which utilize P-TEFb to phosphorylate RNA polymerase II (Pol II) in response to stimuli. Prior to stimulation, a fraction of P-TEFb is recruited t...

journal_title：Molecular cell

authors： McNamara RP,Reeder JE,McMillan EA,Bacon CW,McCann JL,D'Orso I

更新日期：2016-01-07 00:00:00

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

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

abstract：:The essential functions of the conserved Smc5/6 complex remain elusive. To uncover its roles in genome maintenance, we established Saccharomyces cerevisiae cell-cycle-regulated alleles that enable restriction of Smc5/6 components to S or G2/M. Unexpectedly, the essential functions of Smc5/6 segregated fully and select...

journal_title：Molecular cell

authors： Menolfi D,Delamarre A,Lengronne A,Pasero P,Branzei D

更新日期：2015-12-17 00:00:00

abstract：:Poly(ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational modification PAR from substrate NAD(+) to regulate multiple cellular processes. DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is...

journal_title：Molecular cell

authors： Dawicki-McKenna JM,Langelier MF,DeNizio JE,Riccio AA,Cao CD,Karch KR,McCauley M,Steffen JD,Black BE,Pascal JM

更新日期：2015-12-03 00:00:00

abstract：:In a recent paper in Cell Metabolism, Altman et al. (2015) report that MYC disrupts the molecular clock in cancer cells and describe a link between oncogenesis, circadian rhythms, and metabolism. ...

journal_title：Molecular cell

authors： Lau AN,Vander Heiden MG

更新日期：2015-11-19 00:00:00

abstract：:The splitting of chromosomes in anaphase and their delivery into the daughter cells needs to be accurately executed to maintain genome stability. Chromosome splitting requires the degradation of securin, whereas the distribution of the chromosomes into the daughter cells requires the degradation of cyclin B. We show t...

journal_title：Molecular cell

authors： Kamenz J,Mihaljev T,Kubis A,Legewie S,Hauf S

更新日期：2015-11-05 00:00:00

abstract：:Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adaptor protein WDR82 and its assoc...

journal_title：Molecular cell

authors： Austenaa LM,Barozzi I,Simonatto M,Masella S,Della Chiara G,Ghisletti S,Curina A,de Wit E,Bouwman BA,de Pretis S,Piccolo V,Termanini A,Prosperini E,Pelizzola M,de Laat W,Natoli G

更新日期：2015-11-05 00:00:00

abstract：:Phase-separated states of proteins underlie ribonucleoprotein (RNP) granules and nuclear RNA-binding protein assemblies that may nucleate protein inclusions associated with neurodegenerative diseases. We report that the N-terminal low-complexity domain of the RNA-binding protein Fused in Sarcoma (FUS LC) is structural...

journal_title：Molecular cell

authors： Burke KA,Janke AM,Rhine CL,Fawzi NL

更新日期：2015-10-15 00:00:00

abstract：:Elucidating the individual and collaborative functions of genome maintenance factors is critical for understanding how genome duplication is achieved. Here, we investigate a conserved scaffold in budding yeast, Rtt107, and its three partners: a SUMO E3 complex, a ubiquitin E3 complex, and Slx4. Biochemical and genetic...

journal_title：Molecular cell

authors： Hang LE,Peng J,Tan W,Szakal B,Menolfi D,Sheng Z,Lobachev K,Branzei D,Feng W,Zhao X

更新日期：2015-10-15 00:00:00

abstract：:Glaucoma, a blinding neurodegenerative disease, whose risk factors include elevated intraocular pressure (IOP), age, and genetics, is characterized by accelerated and progressive retinal ganglion cell (RGC) death. Despite decades of research, the mechanism of RGC death in glaucoma is still unknown. Here, we demonstrat...

journal_title：Molecular cell

authors： Skowronska-Krawczyk D,Zhao L,Zhu J,Weinreb RN,Cao G,Luo J,Flagg K,Patel S,Wen C,Krupa M,Luo H,Ouyang H,Lin D,Wang W,Li G,Xu Y,Li O,Chung C,Yeh E,Jafari M,Ai M,Zhong Z,Shi W,Zheng L,Krawczyk M,Chen D,Sh

更新日期：2015-09-17 00:00:00

abstract：:Oncogene-induced senescence (OIS) is a tumor-suppressive mechanism typified by stable proliferative arrest, a persistent DNA damage response, and the senescence-associated secretory phenotype (SASP), which helps to maintain the senescent state and triggers bystander senescence in a paracrine fashion. Here, we demonstr...

journal_title：Molecular cell

authors： Chen H,Ruiz PD,McKimpson WM,Novikov L,Kitsis RN,Gamble MJ

更新日期：2015-09-03 00:00:00

abstract：:Autophagy constitutes a prominent mechanism through which eukaryotic cells preserve homeostasis in baseline conditions and in response to perturbations of the intracellular or extracellular microenvironment. Autophagic responses can be relatively non-selective or target a specific subcellular compartment. At least in ...

journal_title：Molecular cell

authors： Sica V,Galluzzi L,Bravo-San Pedro JM,Izzo V,Maiuri MC,Kroemer G

更新日期：2015-08-20 00:00:00

abstract：:Human sister chromatids at metaphase are primarily linked by centromeric cohesion, forming the iconic X shape. Premature loss of centromeric cohesion disrupts orderly mitotic progression. Shugoshin (Sgo1) binds to and protects cohesin at inner centromeres. The kinetochore kinase Bub1 phosphorylates histone H2A at T120...

journal_title：Molecular cell

authors： Liu H,Qu Q,Warrington R,Rice A,Cheng N,Yu H

更新日期：2015-08-06 00:00:00

abstract：:The redundancy of the genetic code implies that most amino acids are encoded by multiple synonymous codons. In all domains of life, a biased frequency of synonymous codons is observed at the genome level, in functionally related genes (e.g., in operons), and within single genes. Other codon bias variants include biase...

journal_title：Molecular cell

authors： Quax TE,Claassens NJ,Söll D,van der Oost J

更新日期：2015-07-16 00:00:00

abstract：:Thousands of cis-elements in genomes are predicted to have vital functions. Although conservation, activity in surrogate assays, polymorphisms, and disease mutations provide functional clues, deletion from endogenous loci constitutes the gold-standard test. A GATA-2-binding, Gata2 intronic cis-element (+9.5) required ...

journal_title：Molecular cell

authors： Hewitt KJ,Kim DH,Devadas P,Prathibha R,Zuo C,Sanalkumar R,Johnson KD,Kang YA,Kim JS,Dewey CN,Keles S,Bresnick EH

更新日期：2015-07-02 00:00:00

abstract：:Stalled replication forks are a critical problem for the cell because they can lead to complex genome rearrangements that underlie cell death and disease. Processes such as DNA damage tolerance and replication fork reversal protect stalled forks from these events. A central mediator of these DNA damage responses in hu...

journal_title：Molecular cell

authors： Kile AC,Chavez DA,Bacal J,Eldirany S,Korzhnev DM,Bezsonova I,Eichman BF,Cimprich KA

更新日期：2015-06-18 00:00:00

abstract：:Small heat shock proteins (sHsps) are ubiquitous molecular chaperones that prevent the aggregation of unfolding proteins during proteotoxic stress. In Caenorhabditis elegans, Sip1 is the only sHsp exclusively expressed in oocytes and embryos. Here, we demonstrate that Sip1 is essential for heat shock survival of repro...

journal_title：Molecular cell

authors： Fleckenstein T,Kastenmüller A,Stein ML,Peters C,Daake M,Krause M,Weinfurtner D,Haslbeck M,Weinkauf S,Groll M,Buchner J

更新日期：2015-06-18 00:00:00

abstract：:ADP-ribosylation is a post-translational modification where single units (mono-ADP-ribosylation) or polymeric chains (poly-ADP-ribosylation) of ADP-ribose are conjugated to proteins by ADP-ribosyltransferases. This post-translational modification and the ADP-ribosyltransferases (also known as PARPs) responsible for it...

journal_title：Molecular cell

authors： Daniels CM,Ong SE,Leung AK

更新日期：2015-06-18 00:00:00

abstract：:Anti-sense transcription originating upstream of mammalian protein-coding genes is a well-documented phenomenon, but remarkably little is known about the regulation or function of anti-sense promoters and the non-coding RNAs they generate. Here we define at nucleotide resolution the divergent transcription start sites...

journal_title：Molecular cell

authors： Scruggs BS,Gilchrist DA,Nechaev S,Muse GW,Burkholder A,Fargo DC,Adelman K

更新日期：2015-06-18 00:00:00

abstract：:Autophagic turnover of intracellular constituents is critical for cellular housekeeping, nutrient recycling, and various aspects of growth and development in eukaryotes. Here we show that autophagy impacts the other major degradative route involving the ubiquitin-proteasome system by eliminating 26S proteasomes, a pro...

journal_title：Molecular cell

authors： Marshall RS,Li F,Gemperline DC,Book AJ,Vierstra RD

更新日期：2015-06-18 00:00:00

abstract：:The Wnt3a/β-catenin and Activin/SMAD2,3 signaling pathways synergize to induce endodermal differentiation of human embryonic stem cells; however, the underlying mechanism is not well understood. Using ChIP-seq and GRO-seq analyses, we show here that Wnt3a-induced β-catenin:LEF-1 enhancers recruit cohesin to direct enh...

journal_title：Molecular cell

authors： Estarás C,Benner C,Jones KA

更新日期：2015-06-04 00:00:00

abstract：:Two publications in the current issue of Cell introduce novel methods for high-throughput single-cell transcriptomics by using droplet microfluidics and sophisticated barcoding schemes for transcriptional profiling of thousands of individual cells. ...

journal_title：Molecular cell

authors： Junker JP,van Oudenaarden A

更新日期：2015-05-21 00:00:00

abstract：:Ubiquitin (UB)-driven signaling systems permeate biology, and are often integrated with other types of post-translational modifications (PTMs), including phosphorylation. Flux through such pathways is dictated by the fractional stoichiometry of distinct modifications and protein assemblies as well as the spatial organ...

journal_title：Molecular cell

authors： Ordureau A,Münch C,Harper JW

更新日期：2015-05-21 00:00:00

abstract：:Transcription is repressed if a DNA double-strand break (DSB) is introduced in close proximity to a transcriptional activation site at least in part by H2A-ubiquitination. While ATM signaling is involved, how it controls H2A-ubiquitination remains unclear. Here, we identify that, in response to DSBs, a transcriptional...

journal_title：Molecular cell

authors： Ui A,Nagaura Y,Yasui A

更新日期：2015-05-07 00:00:00

abstract：:RING ubiquitin ligases (E3) recruit ubiquitin-conjugate enzymes (E2) charged with ubiquitin (Ub) to catalyze ubiquitination. Non-covalent Ub binding to the backside of certain E2s promotes processive polyUb formation, but the mechanism remains elusive. Here, we show that backside bound Ub (Ub(B)) enhances both RING-in...

journal_title：Molecular cell

authors： Buetow L,Gabrielsen M,Anthony NG,Dou H,Patel A,Aitkenhead H,Sibbet GJ,Smith BO,Huang DT

更新日期：2015-04-16 00:00:00

abstract：:In this issue, He et al. (2015) show how herpes virus usurps a cellular metabolic enzyme to induce RIG-I deamidation and RNA-independent activation, likely to better prevent further innate immune responses. ...

journal_title：Molecular cell

authors： Kolakofsky D,Garcin D

更新日期：2015-04-02 00:00:00

abstract：:Bursts of nascent mRNA have been shown to lead to substantial cell-cell variation in unicellular organisms, facilitating diverse responses to environmental challenges. It is unknown whether similar bursts and gene-expression noise occur in mammalian tissues. To address this, we combine single molecule transcript count...

journal_title：Molecular cell

authors： Bahar Halpern K,Tanami S,Landen S,Chapal M,Szlak L,Hutzler A,Nizhberg A,Itzkovitz S

更新日期：2015-04-02 00:00:00

abstract：:Mitochondrial diseases and aging are associated with defects in the oxidative phosphorylation machinery (OXPHOS), which are the only complexes composed of proteins encoded by separate genomes. To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcrip...

journal_title：Molecular cell

authors： Nargund AM,Fiorese CJ,Pellegrino MW,Deng P,Haynes CM

更新日期：2015-04-02 00:00:00

abstract：:The Bloom syndrome helicase BLM and topoisomerase-IIβ-binding protein 1 (TopBP1) are key regulators of genome stability. It was recently proposed that BLM phosphorylation on Ser338 mediates its interaction with TopBP1, to protect BLM from ubiquitylation and degradation (Wang et al., 2013). Here, we show that the BLM-T...

journal_title：Molecular cell

authors： Blackford AN,Nieminuszczy J,Schwab RA,Galanty Y,Jackson SP,Niedzwiedz W

更新日期：2015-03-19 00:00:00

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

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

abstract：:mTOR senses nutrient and energy status to regulate cell survival and metabolism in response to environmental changes. Surprisingly, targeted mutation of Tsc1, a negative regulator of mTORC1, caused a broad reduction in miRNAs due to Drosha degradation. Conversely, targeted mutation of Raptor, an essential component of...

journal_title：Molecular cell

authors： Ye P,Liu Y,Chen C,Tang F,Wu Q,Wang X,Liu CG,Liu X,Liu R,Liu Y,Zheng P

更新日期：2015-02-19 00:00:00

abstract：:The mechanisms contributing to transcription-associated genomic instability are both complex and incompletely understood. Although R-loops are normal transcriptional intermediates, they are also associated with genomic instability. Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of tr...

journal_title：Molecular cell

authors： Hatchi E,Skourti-Stathaki K,Ventz S,Pinello L,Yen A,Kamieniarz-Gdula K,Dimitrov S,Pathania S,McKinney KM,Eaton ML,Kellis M,Hill SJ,Parmigiani G,Proudfoot NJ,Livingston DM

更新日期：2015-02-19 00:00:00

abstract：:The nucleotide (p)ppGpp mediates bacterial stress responses, but its targets and underlying mechanisms of action vary among bacterial species and remain incompletely understood. Here, we characterize the molecular interaction between (p)ppGpp and guanylate kinase (GMK), revealing the importance of this interaction in ...

journal_title：Molecular cell

authors： Liu K,Myers AR,Pisithkul T,Claas KR,Satyshur KA,Amador-Noguez D,Keck JL,Wang JD

更新日期：2015-02-19 00:00:00

abstract：:Curli are extracellular functional amyloids that are assembled by enteric bacteria during biofilm formation and host colonization. An efficient secretion system and chaperone network ensures that the major curli fiber subunit, CsgA, does not form intracellular amyloid aggregates. We discovered that the periplasmic pro...

journal_title：Molecular cell

authors： Evans ML,Chorell E,Taylor JD,Åden J,Götheson A,Li F,Koch M,Sefer L,Matthews SJ,Wittung-Stafshede P,Almqvist F,Chapman MR

更新日期：2015-02-05 00:00:00

abstract：:RNA-mediated gene silencing in human cells requires the accurate generation of ∼22 nt microRNAs (miRNAs) from double-stranded RNA substrates by the endonuclease Dicer. Although the phylogenetically conserved RNA-binding proteins TRBP and PACT are known to contribute to this process, their mode of Dicer binding and the...

journal_title：Molecular cell

authors： Wilson RC,Tambe A,Kidwell MA,Noland CL,Schneider CP,Doudna JA

更新日期：2015-02-05 00:00:00

abstract：:Uncoupling protein 1 (UCP1) mediates nonshivering thermogenesis and, upon cold exposure, is induced in brown adipose tissue (BAT) and subcutaneous white adipose tissue (iWAT). Here, by high-throughput screening using the UCP1 promoter, we identify Zfp516 as a transcriptional activator of UCP1 as well as PGC1α, thereby...

journal_title：Molecular cell

authors： Dempersmier J,Sambeat A,Gulyaeva O,Paul SM,Hudak CS,Raposo HF,Kwan HY,Kang C,Wong RH,Sul HS

更新日期：2015-01-22 00:00:00

abstract：:Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encod...

journal_title：Molecular cell

authors： Raththagala M,Brewer MK,Parker MW,Sherwood AR,Wong BK,Hsu S,Bridges TM,Paasch BC,Hellman LM,Husodo S,Meekins DA,Taylor AO,Turner BD,Auger KD,Dukhande VV,Chakravarthy S,Sanz P,Woods VL Jr,Li S,Vander Kooi CW,Gentry

更新日期：2015-01-22 00:00:00