abstract：:Pre-mRNA splicing relies on the poorly understood dynamic interplay between >150 protein components of the spliceosome. The steps at which splicing can be regulated remain largely unknown. We systematically analyzed the effect of knocking down the components of the splicing machinery on alternative splicing events rel...

journal_title：Molecular cell

authors： Papasaikas P,Tejedor JR,Vigevani L,Valcárcel J

更新日期：2015-01-08 00:00:00

abstract：:During hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into alternative cell fates are not fully understood. Here, we identify cell-fate-determining transcription factors (TFs) governing dendritic cel...

journal_title：Molecular cell

authors： Bornstein C,Winter D,Barnett-Itzhaki Z,David E,Kadri S,Garber M,Amit I

更新日期：2014-12-18 00:00:00

abstract：:R-loops, consisting of an RNA-DNA hybrid and displaced single-stranded DNA, are physiological structures that regulate various cellular processes occurring on chromatin. Intriguingly, changes in R-loop dynamics have also been associated with DNA damage accumulation and genome instability; however, the mechanisms under...

journal_title：Molecular cell

authors： Sollier J,Stork CT,García-Rubio ML,Paulsen RD,Aguilera A,Cimprich KA

更新日期：2014-12-18 00:00:00

abstract：:Unscheduled RNA-DNA hybrids promote the formation DNA double-strand breaks (DSBs) through poorly characterized mechanism. In this issue, Sollier et al. (2014) show that R-loops are processed by XPF and XPG, two structure-specific endonucleases of the NER pathway, to generate DSBs. ...

journal_title：Molecular cell

authors： Lin YL,Pasero P

更新日期：2014-12-18 00:00:00

abstract：:Receptor-interacting protein kinase 3 (RIP3 or RIPK3) has emerged as a central player in necroptosis and a potential target to control inflammatory disease. Here, three selective small-molecule compounds are shown to inhibit RIP3 kinase-dependent necroptosis, although their therapeutic value is undermined by a surpris...

journal_title：Molecular cell

authors： Mandal P,Berger SB,Pillay S,Moriwaki K,Huang C,Guo H,Lich JD,Finger J,Kasparcova V,Votta B,Ouellette M,King BW,Wisnoski D,Lakdawala AS,DeMartino MP,Casillas LN,Haile PA,Sehon CA,Marquis RW,Upton J,Daley-Bauer LP,

更新日期：2014-11-20 00:00:00

abstract：:Metabolic reprogramming is a characteristic of cancer cells. Three studies published in this month's Molecular Cell provide novel insights into the role of mitochondrial pyruvate in tumor metabolism and describe how targeting pyruvate transport and metabolism may afford therapeutic benefit. ...

journal_title：Molecular cell

authors： Szlosarek PW,Lee S,Pollard PJ

更新日期：2014-11-06 00:00:00

abstract：:Macroautophagy (autophagy) is a lysosome-dependent degradation process that has been implicated in age-associated diseases. Autophagy is involved in both cell survival and cell death, but little is known about the mechanisms that distinguish its use during these distinct cell fates. Here, we identify the microRNA miR-...

journal_title：Molecular cell

authors： Nelson C,Ambros V,Baehrecke EH

更新日期：2014-11-06 00:00:00

abstract：:The RNA-guided Cas9 endonuclease specifically targets and cleaves DNA in a sequence-dependent manner and has been widely used for programmable genome editing. Cas9 activity is dependent on interactions with guide RNAs, and evolutionarily divergent Cas9 nucleases have been shown to work orthogonally. However, the molec...

journal_title：Molecular cell

authors： Briner AE,Donohoue PD,Gomaa AA,Selle K,Slorach EM,Nye CH,Haurwitz RE,Beisel CL,May AP,Barrangou R

更新日期：2014-10-23 00:00:00

abstract：:Cellular RNAs can be chemically modified over a hundred different ways. These modifications were once thought to be static, discrete, and utilized to fine-tune RNA structure and function. However, recent studies have revealed that some modifications, like mRNA methylation, can be reversed, and these reversible modific...

journal_title：Molecular cell

authors： Wang X,He C

更新日期：2014-10-02 00:00:00

abstract：:Most colorectal cancers (CRCs) containing activated BRAF (BRAF[V600E]) have a CpG island methylator phenotype (CIMP) characterized by aberrant hypermethylation of many genes, including the mismatch repair gene MLH1. MLH1 silencing results in microsatellite instability and a hypermutable phenotype. Through an RNAi scre...

journal_title：Molecular cell

authors： Fang M,Ou J,Hutchinson L,Green MR

更新日期：2014-09-18 00:00:00

abstract：:Xenopus oocytes can epigenetically reprogram mouse somatic cells toward totipotency. In this issue, Jullien et al. (2014) now describe rapid, interdependent molecular events that facilitate this reprogramming. ...

journal_title：Molecular cell

authors： Maza I,Hanna JH

更新日期：2014-08-21 00:00:00

abstract：:Histone H3K4 demethylase LSD1 plays an important role in stem cell biology, especially in the maintenance of the silencing of differentiation genes. However, how the function of LSD1 is regulated and the differentiation genes are derepressed are not understood. Here, we report that elimination of LSD1 promotes embryon...

journal_title：Molecular cell

authors： Han X,Gui B,Xiong C,Zhao L,Liang J,Sun L,Yang X,Yu W,Si W,Yan R,Yi X,Zhang D,Li W,Li L,Yang J,Wang Y,Sun YE,Zhang D,Meng A,Shang Y

更新日期：2014-08-07 00:00:00

abstract：:The polycomb repressive complex 2 (PRC2) methylates histones for epigenetic silencing and associates with thousands of protein-coding and noncoding RNAs. How the recruitment of PRC2 to specific sites is facilitated is currently unclear. Two recent studies have deciphered the impact of RNA binding on PRC2 recruitment a...

journal_title：Molecular cell

authors： Kretz M,Meister G

更新日期：2014-07-17 00:00:00

abstract：:Eukaryotic cells compartmentalize biochemical processes in different organelles, often relying on metabolic cycles to shuttle reducing equivalents across intracellular membranes. NADPH serves as the electron carrier for the maintenance of redox homeostasis and reductive biosynthesis, with separate cytosolic and mitoch...

journal_title：Molecular cell

authors： Lewis CA,Parker SJ,Fiske BP,McCloskey D,Gui DY,Green CR,Vokes NI,Feist AM,Vander Heiden MG,Metallo CM

更新日期：2014-07-17 00:00:00

abstract：:Heterochromatin is required to restrict aberrant expression of retrotransposons, but it remains poorly defined due to the underlying repeat-rich sequences. We dissected Suv39h-dependent histone H3 lysine 9 trimethylation (H3K9me3) by genome-wide ChIP sequencing in mouse embryonic stem cells (ESCs). Refined bioinformat...

journal_title：Molecular cell

authors： Bulut-Karslioglu A,De La Rosa-Velázquez IA,Ramirez F,Barenboim M,Onishi-Seebacher M,Arand J,Galán C,Winter GE,Engist B,Gerle B,O'Sullivan RJ,Martens JH,Walter J,Manke T,Lachner M,Jenuwein T

更新日期：2014-07-17 00:00:00

abstract：:In bacteria, Hfq is a core RNA chaperone that catalyzes the interaction of mRNAs with regulatory small RNAs (sRNAs). To determine in vivo RNA sequence requirements for Hfq interactions, and to study riboregulation in a bacterial pathogen, Hfq was UV crosslinked to RNAs in enterohemorrhagic Escherichia coli (EHEC). Hfq...

journal_title：Molecular cell

authors： Tree JJ,Granneman S,McAteer SP,Tollervey D,Gally DL

更新日期：2014-07-17 00:00:00

abstract：:In this issue of Molecular Cell, Guo et al. (2014) report that misfolded or aggregated nuclear proteins, such as pathogenic polyQ proteins, are cleared by a SUMO-dependent quality control pathway, which involves the E3 SUMO ligase PML and the SUMO-targeted ubiquitin ligase RNF4. ...

journal_title：Molecular cell

authors： Gärtner A,Muller S

更新日期：2014-07-03 00:00:00

abstract：:To exert regulatory function, miRNAs guide Argonaute (AGO) proteins to partially complementary sites on target RNAs. Crosslinking and immunoprecipitation (CLIP) assays are state-of-the-art to map AGO binding sites, but assigning the targeting miRNA to these sites relies on bioinformatics predictions and is therefore i...

journal_title：Molecular cell

authors： Grosswendt S,Filipchyk A,Manzano M,Klironomos F,Schilling M,Herzog M,Gottwein E,Rajewsky N

更新日期：2014-06-19 00:00:00

abstract：:CCR4-NOT is a major effector complex in miRNA-mediated gene silencing. It is recruited to miRNA targets through interactions with tryptophan (W)-containing motifs in TNRC6/GW182 proteins and is required for both translational repression and degradation of miRNA targets. Here, we elucidate the structural basis for the ...

journal_title：Molecular cell

authors： Chen Y,Boland A,Kuzuoğlu-Öztürk D,Bawankar P,Loh B,Chang CT,Weichenrieder O,Izaurralde E

更新日期：2014-06-05 00:00:00

abstract：:The proper processing, export, localization, translation, and degradation of mRNAs are necessary for regulation of gene expression. These processes are controlled by mRNA-specific regulatory proteins, noncoding RNAs, and core machineries common to most mRNAs. These factors bind the mRNA in large complexes known as mes...

journal_title：Molecular cell

authors： Mitchell SF,Parker R

更新日期：2014-05-22 00:00:00

abstract：:Canonical Wnt signaling is thought to regulate cell behavior mainly by inducing β-catenin-dependent transcription of target genes. In proliferating cells Wnt signaling peaks in the G2/M phase of the cell cycle, but the significance of this "mitotic Wnt signaling" is unclear. Here we introduce Wnt-dependent stabilizati...

journal_title：Molecular cell

authors： Acebron SP,Karaulanov E,Berger BS,Huang YL,Niehrs C

更新日期：2014-05-22 00:00:00

abstract：:The tumor suppressor BAP1 interacts with chromatin-associated proteins and regulates cell proliferation, but its mechanism of action and regulation remain poorly defined. We show that the ubiquitin-conjugating enzyme UBE2O multi-monoubiquitinates the nuclear localization signal of BAP1, thereby inducing its cytoplasmi...

journal_title：Molecular cell

authors： Mashtalir N,Daou S,Barbour H,Sen NN,Gagnon J,Hammond-Martel I,Dar HH,Therrien M,Affar el B

更新日期：2014-05-08 00:00:00

abstract：:In this issue of Molecular Cell, Chen et al. (2014) provide evidence that FMRP represses translation by binding the ribosome, suggesting a novel form of translational control. ...

journal_title：Molecular cell

authors： Harigaya Y,Parker R

更新日期：2014-05-08 00:00:00

abstract：:Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced...

journal_title：Molecular cell

authors： Savage KI,Gorski JJ,Barros EM,Irwin GW,Manti L,Powell AJ,Pellagatti A,Lukashchuk N,McCance DJ,McCluggage WG,Schettino G,Salto-Tellez M,Boultwood J,Richard DJ,McDade SS,Harkin DP

更新日期：2014-05-08 00:00:00

abstract：:Despite being sessile organisms constantly exposed to potential pathogens and pests, plants are surprisingly resilient to infections. Plants can detect invaders via the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). Plant PRRs are surface-localized receptor-like ...

journal_title：Molecular cell

authors： Macho AP,Zipfel C

更新日期：2014-04-24 00:00:00

abstract：:Staphylococcus aureus virulence is regulated when secreted autoinducing peptides (AIPs) are recognized by a membrane-bound receptor histidine kinase (RHK), AgrC. Some AIPs are agonists of virulence gene expression, while others are antagonists. It is unclear how AIP binding regulates AgrC activity. Here, we reconstitu...

journal_title：Molecular cell

authors： Wang B,Zhao A,Novick RP,Muir TW

更新日期：2014-03-20 00:00:00

abstract：:The circadian clock is a self-sustaining oscillator that controls daily rhythms. For the proper circadian gene expression, dynamic changes in chromatin structure are important. Although chromatin modifiers have been shown to play a role in circadian gene expression, the in vivo role of circadian signal-modulated chrom...

journal_title：Molecular cell

authors： Nam HJ,Boo K,Kim D,Han DH,Choe HK,Kim CR,Sun W,Kim H,Kim K,Lee H,Metzger E,Schuele R,Yoo SH,Takahashi JS,Cho S,Son GH,Baek SH

更新日期：2014-03-06 00:00:00

abstract：:Nucleosomes are barriers to transcription in vitro; however, their effects on RNA polymerase in vivo are unknown. Here we describe a simple and general strategy to comprehensively map the positions of elongating and arrested RNA polymerase II (RNAPII) at nucleotide resolution. We find that the entry site of the first ...

journal_title：Molecular cell

authors： Weber CM,Ramachandran S,Henikoff S

更新日期：2014-03-06 00:00:00

abstract：:The response to endoplasmic reticulum (ER) stress relies on activation of unfolded protein response (UPR) sensors, and the outcome of the UPR depends on the duration and strength of signal. Here, we demonstrate a mechanism that attenuates the activity of the UPR sensor inositol-requiring enzyme 1α (IRE1α). A resident ...

journal_title：Molecular cell

authors： Eletto D,Eletto D,Dersh D,Gidalevitz T,Argon Y

更新日期：2014-02-20 00:00:00

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

authors： Kundu M

更新日期：2014-02-20 00:00:00

abstract：:The displacement loop (D loop) is the product of homology search and DNA strand invasion, constituting a central intermediate in homologous recombination (HR). In eukaryotes, the Rad51 DNA strand exchange protein is assisted in D loop formation by the Rad54 motor protein. Curiously, Rad54 also disrupts D loops. How th...

journal_title：Molecular cell

authors： Wright WD,Heyer WD

更新日期：2014-02-06 00:00:00

abstract：:Given the intimate link between inflammation and dysregulated cell proliferation in cancer, we investigated cytokine-triggered gene expression in different cell cycle stages. Transcriptome analysis revealed that G1 release through cyclin-dependent kinase 6 (CDK6) and CDK4 primes and cooperates with the cytokine-driven...

journal_title：Molecular cell

authors： Handschick K,Beuerlein K,Jurida L,Bartkuhn M,Müller H,Soelch J,Weber A,Dittrich-Breiholz O,Schneider H,Scharfe M,Jarek M,Stellzig J,Schmitz ML,Kracht M

更新日期：2014-01-23 00:00:00

abstract：:In this issue, Song et al. (2014) describe how microtubules and the RAN GTPase/importin-β system collaborate to control timing of HURP action and its turnover via the anaphase promoting complex (APC)-proteasome system, thereby ensuring temporal control of late mitotic events. ...

journal_title：Molecular cell

authors： Vaites LL,Harper JW

更新日期：2014-01-23 00:00:00

abstract：:MRE11 within the MRE11-RAD50-NBS1 (MRN) complex acts in DNA double-strand break repair (DSBR), detection, and signaling; yet, how its endo- and exonuclease activities regulate DSBR by nonhomologous end-joining (NHEJ) versus homologous recombination (HR) remains enigmatic. Here, we employed structure-based design with ...

journal_title：Molecular cell

authors： Shibata A,Moiani D,Arvai AS,Perry J,Harding SM,Genois MM,Maity R,van Rossum-Fikkert S,Kertokalio A,Romoli F,Ismail A,Ismalaj E,Petricci E,Neale MJ,Bristow RG,Masson JY,Wyman C,Jeggo PA,Tainer JA

更新日期：2014-01-09 00:00:00

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

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

abstract：:Folding-defective proteins must be cleared efficiently from the endoplasmic reticulum (ER) to prevent perturbation of the folding environment and to maintain cellular proteostasis. Misfolded proteins engage dislocation machineries (dislocons) built around E3 ubiquitin ligases that promote their transport across the ER...

journal_title：Molecular cell

authors： Bernasconi R,Galli C,Kokame K,Molinari M

更新日期：2013-12-26 00:00:00

abstract：:Faithful copying of the genome is essential for life. In eukaryotes, a single archaeo-eukaryotic primase (AEP), DNA primase, is required for the initiation and progression of DNA replication. Here we have identified additional eukaryotic AEP-like proteins with DNA-dependent primase and/or polymerase activity. Uniquely...

journal_title：Molecular cell

authors： Rudd SG,Glover L,Jozwiakowski SK,Horn D,Doherty AJ

更新日期：2013-11-21 00:00:00

abstract：:The selective degradation of intracellular components by autophagy involves sequential interactions of the cargo with a receptor, which also binds the autophagosomal protein Atg8 and a scaffold protein. Here, we demonstrated that mutations in C. elegans epg-11, which encodes an arginine methyltransferase homologous to...

journal_title：Molecular cell

authors： Li S,Yang P,Tian E,Zhang H

更新日期：2013-11-07 00:00:00

abstract：:BRAF is an oncogenic protein kinase that drives cell growth and proliferation through the MEK-ERK signaling pathway. BRAF inhibitors have demonstrated antitumor efficacy in melanoma therapy but have also been found to be associated with the development of cutaneous squamous cell carcinomas (cSCCs) in certain patients....

journal_title：Molecular cell

authors： Shen CH,Yuan P,Perez-Lorenzo R,Zhang Y,Lee SX,Ou Y,Asara JM,Cantley LC,Zheng B

更新日期：2013-10-24 00:00:00

abstract：:Homology-dependent repair of double-strand breaks (DSBs) from nonsister templates has the potential to generate loss of heterozygosity or genome rearrangements. Here we show that the Saccharomyces cerevisiae Mph1 helicase prevents crossovers between ectopic sequences by removing substrates for Mus81-Mms4 or Rad1-Rad10...

journal_title：Molecular cell

authors： Mazón G,Symington LS

更新日期：2013-10-10 00:00:00