abstract：:The biosynthesis of coenzyme Q presents a paradigm for how cells surmount hydrophobic barriers in lipid biology. In eukaryotes, CoQ precursors-among nature's most hydrophobic molecules-must somehow be presented to a series of enzymes peripherally associated with the mitochondrial inner membrane. Here, we reveal that t...

journal_title：Molecular cell

authors： Lohman DC,Aydin D,Von Bank HC,Smith RW,Linke V,Weisenhorn E,McDevitt MT,Hutchins P,Wilkerson EM,Wancewicz B,Russell J,Stefely MS,Beebe ET,Jochem A,Coon JJ,Bingman CA,Dal Peraro M,Pagliarini DJ

更新日期：2019-02-21 00:00:00

abstract：:Multisite phosphorylation of kinases can induce on-off or graded regulation of catalytic activity; however, its influence on substrate specificity remains unclear. Here, we show that multisite phosphorylation of ribosomal protein S6 kinase 1 (S6K1) alters target selection. Agonist-inducible phosphorylation of glutamyl...

journal_title：Molecular cell

authors： Arif A,Jia J,Willard B,Li X,Fox PL

更新日期：2019-02-07 00:00:00

abstract：:CRISPR-Cas12a (Cpf1) is an RNA-guided DNA-cutting nuclease that has been repurposed for genome editing. Upon target DNA binding, Cas12a cleaves both the target DNA in cis and non-target single-stranded DNAs (ssDNAs) in trans. To elucidate the molecular basis for both DNase cleavage modes, we performed structural and b...

journal_title：Molecular cell

authors： Swarts DC,Jinek M

更新日期：2019-02-07 00:00:00

abstract：:In this issue of Molecular Cell,Sharma et al. (2019) show that normal cell growth requires conversion of an arginine residue in the RNA polymerase II C-terminal domain (CTD) to citrulline, uncovering a potential regulatory pathway involving opposing arginine modifications. ...

journal_title：Molecular cell

authors： Corden JL

更新日期：2019-01-03 00:00:00

abstract：:Transcription initiation requires opening of promoter DNA in the RNA polymerase II (Pol II) pre-initiation complex (PIC), but it remains unclear how this is achieved. Here we report the cryo-electron microscopic (cryo-EM) structure of a yeast PIC that contains underwound, distorted promoter DNA in the closed Pol II cl...

journal_title：Molecular cell

authors： Dienemann C,Schwalb B,Schilbach S,Cramer P

更新日期：2019-01-03 00:00:00

abstract：:Mutations that lead to splicing defects can have severe consequences on gene function and cause disease. Here, we explore how human genetic variation affects exon recognition by developing a multiplexed functional assay of splicing using Sort-seq (MFASS). We assayed 27,733 variants in the Exome Aggregation Consortium ...

journal_title：Molecular cell

authors： Cheung R,Insigne KD,Yao D,Burghard CP,Wang J,Hsiao YE,Jones EM,Goodman DB,Xiao X,Kosuri S

更新日期：2019-01-03 00:00:00

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

authors： Noe Gonzalez M,Conaway RC,Conaway JW

更新日期：2018-12-06 00:00:00

abstract：:mRNAs form ribonucleoprotein complexes (mRNPs) by association with proteins that are crucial for mRNA metabolism. While the mRNP proteome has been well characterized, little is known about mRNP organization. Using a single-molecule approach, we show that mRNA conformation changes depending on its cellular localization...

journal_title：Molecular cell

authors： Adivarahan S,Livingston N,Nicholson B,Rahman S,Wu B,Rissland OS,Zenklusen D

更新日期：2018-11-15 00:00:00

abstract：:DNA replication is initiated by assembly of the kinase cell division cycle 7 (CDC7) with its regulatory activation subunit, activator of S-phase kinase (ASK), to activate DNA helicase. However, the mechanism underlying regulation of CDC7-ASK complex is unclear. Here, we show that ADP generated from CDC7-mediated MCM p...

journal_title：Molecular cell

authors： Li X,Qian X,Jiang H,Xia Y,Zheng Y,Li J,Huang BJ,Fang J,Qian CN,Jiang T,Zeng YX,Lu Z

更新日期：2018-11-15 00:00:00

abstract：:Protein phase separation by low-complexity, intrinsically disordered domains generates membraneless organelles and links to neurodegeneration. Cellular prion protein (PrPC) contains such domains, causes spongiform degeneration, and is a receptor for Alzheimer's amyloid-β oligomers (Aβo). Here, we show that PrPC separa...

journal_title：Molecular cell

authors： Kostylev MA,Tuttle MD,Lee S,Klein LE,Takahashi H,Cox TO,Gunther EC,Zilm KW,Strittmatter SM

更新日期：2018-11-01 00:00:00

abstract：:Copy-number changes generate phenotypic variability in health and disease. Whether organisms protect against copy-number changes is largely unknown. Here, we show that Saccharomyces cerevisiae monitors the copy number of its ribosomal DNA (rDNA) and rapidly responds to copy-number loss with the clonal amplification of...

journal_title：Molecular cell

authors： Mansisidor A,Molinar T Jr,Srivastava P,Dartis DD,Pino Delgado A,Blitzblau HG,Klein H,Hochwagen A

更新日期：2018-11-01 00:00:00

abstract：:Productive splicing of human precursor messenger RNAs (pre-mRNAs) requires the correct selection of authentic splice sites (SS) from the large pool of potential SS. Although SS consensus sequence and splicing regulatory proteins are known to influence SS usage, the mechanisms ensuring the effective suppression of cryp...

journal_title：Molecular cell

authors： Boehm V,Britto-Borges T,Steckelberg AL,Singh KK,Gerbracht JV,Gueney E,Blazquez L,Altmüller J,Dieterich C,Gehring NH

更新日期：2018-11-01 00:00:00

abstract：:Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death can be triggered by defects in chromosome synapsis and recombination, which involve repair of DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oo...

journal_title：Molecular cell

authors： Qiao H,Rao HBDP,Yun Y,Sandhu S,Fong JH,Sapre M,Nguyen M,Tham A,Van BW,Chng TYH,Lee A,Hunter N

更新日期：2018-10-18 00:00:00

abstract：:In this issue of Molecular Cell, Han et al. (2018) show that phosphatidic acid inhibits the action of the LATS kinases, key mediators of Hippo pathway signaling, which leads to an increase in the nuclear activity of the transcriptional regulator YAP. ...

journal_title：Molecular cell

authors： Stampouloglou E,Varelas X

更新日期：2018-10-18 00:00:00

abstract：:Alternative splicing (AS) is a widespread process underlying the generation of transcriptomic and proteomic diversity and is frequently misregulated in human disease. Accordingly, an important goal of biomedical research is the development of tools capable of comprehensively, accurately, and efficiently profiling AS. ...

journal_title：Molecular cell

authors： Sterne-Weiler T,Weatheritt RJ,Best AJ,Ha KCH,Blencowe BJ

更新日期：2018-10-04 00:00:00

abstract：:Protein kinase RNA-activated (PKR) induces immune response by sensing viral double-stranded RNAs (dsRNAs). However, growing evidence suggests that PKR can also be activated by endogenously expressed dsRNAs. Here, we capture these dsRNAs by formaldehyde-mediated crosslinking and immunoprecipitation sequencing and find ...

journal_title：Molecular cell

authors： Kim Y,Park J,Kim S,Kim M,Kang MG,Kwak C,Kang M,Kim B,Rhee HW,Kim VN

更新日期：2018-09-20 00:00:00

abstract：:β-hydroxybutyrate (β-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether β-HB alters the senescence pathway in vascular cells remains unknown. Here we report that β-HB promotes vascular cell quiescence, which signi...

journal_title：Molecular cell

authors： Han YM,Bedarida T,Ding Y,Somba BK,Lu Q,Wang Q,Song P,Zou MH

更新日期：2018-09-20 00:00:00

abstract：:Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin's role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and...

journal_title：Molecular cell

authors： Cha JH,Yang WH,Xia W,Wei Y,Chan LC,Lim SO,Li CW,Kim T,Chang SS,Lee HH,Hsu JL,Wang HL,Kuo CW,Chang WC,Hadad S,Purdie CA,McCoy AM,Cai S,Tu Y,Litton JK,Mittendorf EA,Moulder SL,Symmans WF,Thompson AM,Piwnica-

更新日期：2018-08-16 00:00:00

abstract：:Many mechanisms contribute to regulation of gene expression to ensure coordinated cellular behaviors and fate decisions. Transcriptional responses to external signals can consist of many hundreds of genes that can be parsed into different categories based on kinetics of induction, cell-type and signal specificity, and...

journal_title：Molecular cell

authors： Pope SD,Medzhitov R

更新日期：2018-08-02 00:00:00

abstract：:Covalently closed circular RNAs (circRNAs) are produced by precursor mRNA back-splicing of exons of thousands of genes in eukaryotes. circRNAs are generally expressed at low levels and often exhibit cell-type-specific and tissue-specific patterns. Recent studies have shown that their biogenesis requires spliceosomal m...

journal_title：Molecular cell

authors： Li X,Yang L,Chen LL

更新日期：2018-08-02 00:00:00

abstract：:The ribosome, a ribonucleoprotein machine for protein synthesis, can also serve as an abundant nutrient source under starvation conditions. In a recent issue of Science, Wyant et al. (2018) discovered a specialized "spoon" to "scoop up" more ribosomes for degradation by autophagy. ...

journal_title：Molecular cell

authors： Nakatogawa H

更新日期：2018-07-19 00:00:00

abstract：:tRNAs are subject to numerous modifications, including methylation. Mutations in the human N7-methylguanosine (m7G) methyltransferase complex METTL1/WDR4 cause primordial dwarfism and brain malformation, yet the molecular and cellular function in mammals is not well understood. We developed m7G methylated tRNA immunop...

journal_title：Molecular cell

authors： Lin S,Liu Q,Lelyveld VS,Choe J,Szostak JW,Gregory RI

更新日期：2018-07-19 00:00:00

abstract：:Mitochondrial protein import stress compromises functioning of the organelles, due to inadequate supply of inner mitochondrial proteins. Weidberg and Amon (2018) describe a new monitoring pathway in budding yeast, which restores mitochondrial function following the clearing of accumulated unfolded pre-transported mito...

journal_title：Molecular cell

authors： Desai R,Campanella M

更新日期：2018-07-05 00:00:00

abstract：:Interphase chromatin is organized into topologically associating domains (TADs). Within TADs, chromatin looping interactions are formed between DNA regulatory elements, but their functional importance for the establishment of the 3D genome organization and gene regulation during development is unclear. Using high-reso...

journal_title：Molecular cell

authors： Ogiyama Y,Schuettengruber B,Papadopoulos GL,Chang JM,Cavalli G

更新日期：2018-07-05 00:00:00

abstract：:DNA replication introduces a dosage imbalance between early and late replicating genes. In budding yeast, buffering gene expression against this imbalance depends on marking replicated DNA by H3K56 acetylation (H3K56ac). Whether additional processes are required for suppressing transcription from H3K56ac-labeled DNA r...

journal_title：Molecular cell

authors： Voichek Y,Mittelman K,Gordon Y,Bar-Ziv R,Lifshitz Smit D,Shenhav R,Barkai N

更新日期：2018-06-21 00:00:00

abstract：:When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activi...

journal_title：Molecular cell

authors： Szoradi T,Schaeff K,Garcia-Rivera EM,Itzhak DN,Schmidt RM,Bircham PW,Leiss K,Diaz-Miyar J,Chen VK,Muzzey D,Borner GHH,Schuck S

更新日期：2018-06-21 00:00:00

abstract：:Spt6 is an essential histone chaperone that mediates nucleosome reassembly during gene transcription. Spt6 also associates with RNA polymerase II (RNAPII) via a tandem Src2 homology domain. However, the significance of Spt6-RNAPII interaction is not well understood. Here, we show that Spt6 recruitment to genes and the...

journal_title：Molecular cell

authors： Dronamraju R,Hepperla AJ,Shibata Y,Adams AT,Magnuson T,Davis IJ,Strahl BD

更新日期：2018-06-21 00:00:00

abstract：:Takahashi et al. (2018) report that the peptide CLE25 together with the BAM1, BAM3 LRR receptor-like kinases are involved in root-to-shoot communication during dehydration stress in Arabidopsis. ...

journal_title：Molecular cell

authors： McLachlan DH,Pridgeon AJ,Hetherington AM

更新日期：2018-06-21 00:00:00

abstract：:Cas4 nucleases are conserved factors in many CRISPR systems, yet their molecular role has remained enigmatic. In this issue of Molecular Cell, Shiimori et al. (2018) report that two Cas4 nucleases together determine the size, orientation, and PAM for foreign DNA snippets acquired by CRISPR loci as immunological memory...

journal_title：Molecular cell

authors： Hou Z,Zhang Y

更新日期：2018-06-07 00:00:00

abstract：:Necroptosis is an important form of lytic cell death triggered by injury and infection, but whether mixed lineage kinase domain-like (MLKL) is sufficient to execute this pathway is unknown. In a genetic selection for human cell mutants defective for MLKL-dependent necroptosis, we identified mutations in IPMK and ITPK1...

journal_title：Molecular cell

authors： Dovey CM,Diep J,Clarke BP,Hale AT,McNamara DE,Guo H,Brown NW Jr,Cao JY,Grace CR,Gough PJ,Bertin J,Dixon SJ,Fiedler D,Mocarski ES,Kaiser WJ,Moldoveanu T,York JD,Carette JE

更新日期：2018-06-07 00:00:00

abstract：:Stress granules (SGs) are cytoplasmic assemblies of mRNPs stalled in translation initiation. They are induced by various stress conditions, including exposure to the environmental toxin and carcinogen arsenic. While perturbed SG turnover is linked to the pathogenesis of neurodegenerative diseases, the molecular mechan...

journal_title：Molecular cell

authors： Turakhiya A,Meyer SR,Marincola G,Böhm S,Vanselow JT,Schlosser A,Hofmann K,Buchberger A

更新日期：2018-06-07 00:00:00

abstract：:Animal cells have a remarkable capacity to adopt durable and heritable gene expression programs or epigenetic states that define the physical properties and diversity of somatic cell types. The maintenance of epigenetic programs depends on poorly understood pathways that prevent gain or loss of inherited signals. In t...

journal_title：Molecular cell

authors： Ishidate T,Ozturk AR,Durning DJ,Sharma R,Shen EZ,Chen H,Seth M,Shirayama M,Mello CC

更新日期：2018-05-17 00:00:00

abstract：:Nutrients are not only organic compounds fueling bioenergetics and biosynthesis, but also key chemical signals controlling growth and metabolism. Nutrients enormously impact the production of reactive oxygen species (ROS), which play essential roles in normal physiology and diseases. How nutrient signaling is integrat...

journal_title：Molecular cell

authors： Tsang CK,Chen M,Cheng X,Qi Y,Chen Y,Das I,Li X,Vallat B,Fu LW,Qian CN,Wang HY,White E,Burley SK,Zheng XFS

更新日期：2018-05-03 00:00:00

abstract：:Gcn4 is a yeast transcriptional activator induced by amino acid starvation. ChIP-seq analysis revealed 546 genomic sites occupied by Gcn4 in starved cells, representing ∼30% of Gcn4-binding motifs. Surprisingly, only ∼40% of the bound sites are in promoters, of which only ∼60% activate transcription, indicating extens...

journal_title：Molecular cell

authors： Rawal Y,Chereji RV,Valabhoju V,Qiu H,Ocampo J,Clark DJ,Hinnebusch AG

更新日期：2018-04-19 00:00:00

abstract：:EGFR activates phosphatidylinositide 3-kinase (PI3K), but the mechanism underlying this activation is not completely understood. We demonstrated here that EGFR activation resulted in lysine acetyltransferase 5 (KAT5)-mediated K395 acetylation of the platelet isoform of phosphofructokinase 1 (PFKP) and subsequent trans...

journal_title：Molecular cell

authors： Lee JH,Liu R,Li J,Wang Y,Tan L,Li XJ,Qian X,Zhang C,Xia Y,Xu D,Guo W,Ding Z,Du L,Zheng Y,Chen Q,Lorenzi PL,Mills GB,Jiang T,Lu Z

更新日期：2018-04-19 00:00:00

abstract：:Growing resistance of pathogenic bacteria and shortage of antibiotic discovery platforms challenge the use of antibiotics in the clinic. This threat calls for exploration of unconventional sources of antibiotics and identification of inhibitors able to eradicate resistant bacteria. Here we describe a different class o...

journal_title：Molecular cell

authors： Pantel L,Florin T,Dobosz-Bartoszek M,Racine E,Sarciaux M,Serri M,Houard J,Campagne JM,de Figueiredo RM,Midrier C,Gaudriault S,Givaudan A,Lanois A,Forst S,Aumelas A,Cotteaux-Lautard C,Bolla JM,Vingsbo Lundberg C,Huseby

更新日期：2018-04-05 00:00:00

abstract：:Fidaxomicin is an antibacterial drug in clinical use for treatment of Clostridium difficile diarrhea. The active ingredient of fidaxomicin, lipiarmycin A3 (Lpm), functions by inhibiting bacterial RNA polymerase (RNAP). Here we report a cryo-EM structure of Mycobacterium tuberculosis RNAP holoenzyme in complex with Lpm...

journal_title：Molecular cell

authors： Lin W,Das K,Degen D,Mazumder A,Duchi D,Wang D,Ebright YW,Ebright RY,Sineva E,Gigliotti M,Srivastava A,Mandal S,Jiang Y,Liu Y,Yin R,Zhang Z,Eng ET,Thomas D,Donadio S,Zhang H,Zhang C,Kapanidis AN,Ebright RH

更新日期：2018-04-05 00:00:00

abstract：:In this issue of Molecular Cell, Roh et al. (2018) present a high-resolution cryo-EM structure of the nanodisc-reconstituted yeast Vo proton channel that provides important new insights into subunit arrangements and the proton translocation pathway in V-type ATPases. ...

journal_title：Molecular cell

authors： Muench SP,van der Laan M

更新日期：2018-03-15 00:00:00

abstract：:PRDM9 determines the localization of meiotic recombination hotspots, which are associated with histone H3 methylation. It is not known whether PRDM9's methyltransferase activity is required or how some PRDM9 alleles can dominate the distribution of hotspots over other alleles. Diagouraga, Clément, and colleagues (2018...

journal_title：Molecular cell

authors： Kang R,Zelazowski MJ,Cole F

更新日期：2018-03-01 00:00:00

abstract：:Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in ...

journal_title：Molecular cell

authors： Tsai PI,Lin CH,Hsieh CH,Papakyrikos AM,Kim MJ,Napolioni V,Schoor C,Couthouis J,Wu RM,Wszolek ZK,Winter D,Greicius MD,Ross OA,Wang X

更新日期：2018-03-01 00:00:00