abstract：:Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bo...

journal_title：Molecular cell

authors： Ma S,Shen Q,Zhao LH,Mao C,Zhou XE,Shen DD,de Waal PW,Bi P,Li C,Jiang Y,Wang MW,Sexton PM,Wootten D,Melcher K,Zhang Y,Xu HE

更新日期：2020-02-06 00:00:00

abstract：:A recent paper by Gallagher et al. (2020) demonstrates that c-di-GMP controls spore formation in Streptomyces venezuelae through sequestering the sporulation sigma factor σWhiG and presents the crystal structure of a ternary complex between c-di-GMP, σWhiG, and its anti-sigma factor, RsiG. ...

journal_title：Molecular cell

authors： Chou SH,Galperin MY

更新日期：2020-02-06 00:00:00

abstract：:TMEM39A, encoding an ER-localized transmembrane protein, is a susceptibility locus for multiple autoimmune diseases. The molecular function of TMEM39A remains completely unknown. Here we demonstrated that TMEM39A, also called SUSR2, modulates autophagy activity by regulating the spatial distribution and levels of PtdI...

journal_title：Molecular cell

authors： Miao G,Zhang Y,Chen D,Zhang H

更新日期：2020-02-06 00:00:00

abstract：:N6-methyladenosine (m6A), the most abundant internal mRNA modification, and N6,2'-O-dimethyladenosine (m6Am), found at the first-transcribed nucleotide, are two reversible epitranscriptomic marks. However, the profiles and distribution patterns of m6A and m6Am across human and mouse tissues are poorly characterized. H...

journal_title：Molecular cell

authors： Liu J,Li K,Cai J,Zhang M,Zhang X,Xiong X,Meng H,Xu X,Huang Z,Peng J,Fan J,Yi C

更新日期：2020-01-16 00:00:00

abstract：:The genomes of mammalian neurons contain uniquely high levels of non-CG DNA methylation that can be bound by the Rett syndrome protein, MeCP2, to regulate gene expression. How patterns of non-CG methylation are established in neurons and the mechanism by which this methylation works with MeCP2 to control gene expressi...

journal_title：Molecular cell

authors： Clemens AW,Wu DY,Moore JR,Christian DL,Zhao G,Gabel HW

更新日期：2020-01-16 00:00:00

abstract：:FUS is a nuclear RNA-binding protein, and its cytoplasmic aggregation is a pathogenic signature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It remains unknown how the FUS-RNA interactions contribute to phase separation and whether its phase behavior is affected by ALS-linked mutations. He...

journal_title：Molecular cell

authors： Niaki AG,Sarkar J,Cai X,Rhine K,Vidaurre V,Guy B,Hurst M,Lee JC,Koh HR,Guo L,Fare CM,Shorter J,Myong S

更新日期：2020-01-02 00:00:00

abstract：:The inner nuclear membrane (INM) is continuous with the endoplasmic reticulum (ER) but harbors a distinctive proteome essential for nuclear functions. In yeast, the Asi1/Asi2/Asi3 ubiquitin ligase complex safeguards the INM proteome through the clearance of mislocalized ER membrane proteins. How the Asi complex select...

journal_title：Molecular cell

authors： Natarajan N,Foresti O,Wendrich K,Stein A,Carvalho P

更新日期：2020-01-02 00:00:00

abstract：:High-resolution Cas9 structures have yet to reveal catalytic conformations due to HNH nuclease domain positioning away from the cleavage site. Nme1Cas9 and Nme2Cas9 are compact nucleases for in vivo genome editing. Here, we report structures of meningococcal Cas9 homologs in complex with sgRNA, dsDNA, or the AcrIIC3 a...

journal_title：Molecular cell

authors： Sun W,Yang J,Cheng Z,Amrani N,Liu C,Wang K,Ibraheim R,Edraki A,Huang X,Wang M,Wang J,Liu L,Sheng G,Yang Y,Lou J,Sontheimer EJ,Wang Y

更新日期：2019-12-19 00:00:00

abstract：:In this issue of Molecular Cell, Terrell et al. (2019) characterize the interactions of RAS-RAF complexes in live cells. Using bioluminescence resonance energy transfer (BRET) technology, they show that individual RAF family members exhibit distinct binding affinities to each RAS family protein, with CRAF exhibiting h...

journal_title：Molecular cell

authors： Venkatanarayan A,Malek S

更新日期：2019-12-19 00:00:00

abstract：:MYOD-directed fibroblast trans-differentiation into skeletal muscle provides a unique model to investigate how one transcription factor (TF) reconfigures the three-dimensional chromatin architecture to control gene expression, which is otherwise achieved by the combinatorial activities of multiple TFs. Integrative ana...

journal_title：Molecular cell

authors： Dall'Agnese A,Caputo L,Nicoletti C,di Iulio J,Schmitt A,Gatto S,Diao Y,Ye Z,Forcato M,Perera R,Bicciato S,Telenti A,Ren B,Puri PL

更新日期：2019-11-07 00:00:00

abstract：:Stress granules and P-bodies are cytosolic biomolecular condensates that dynamically form by the phase separation of RNAs and proteins. They participate in translational control and buffer the proteome. Upon stress, global translation halts and mRNAs bound to the translational machinery and other proteins coalesce to ...

journal_title：Molecular cell

authors： Youn JY,Dyakov BJA,Zhang J,Knight JDR,Vernon RM,Forman-Kay JD,Gingras AC

更新日期：2019-10-17 00:00:00

abstract：:Alternative lengthening of telomeres (ALT) is a homology-directed repair (HDR) mechanism of telomere elongation that controls proliferation in aggressive cancers. We show that the disruption of RAD51-associated protein 1 (RAD51AP1) in ALT+ cancer cells leads to generational telomere shortening. This is due to RAD51AP1...

journal_title：Molecular cell

authors： Barroso-González J,García-Expósito L,Hoang SM,Lynskey ML,Roncaioli JL,Ghosh A,Wallace CT,de Vitis M,Modesti M,Bernstein KA,Sarkar SN,Watkins SC,O'Sullivan RJ

更新日期：2019-10-03 00:00:00

abstract：:Cancer cells acquire unlimited proliferative capacity by either re-expressing telomerase or inducing alternative lengthening of telomeres (ALT), which relies on telomere recombination. Here, we show that ALT recombination requires coordinate regulation of the SMX and BTR complexes to ensure the appropriate balance of ...

journal_title：Molecular cell

authors： Panier S,Maric M,Hewitt G,Mason-Osann E,Gali H,Dai A,Labadorf A,Guervilly JH,Ruis P,Segura-Bayona S,Belan O,Marzec P,Gaillard PL,Flynn RL,Boulton SJ

更新日期：2019-10-03 00:00:00

abstract：:High plasticity to utilize different nutrients to adapt metabolic stress is one of the hallmarks for cancer cells. However, the underlying mechanisms by which cancer cells reprogram metabolic machinery in response to metabolic stress remain largely unclear. In this issue of Molecular Cell, Wang et al. (2019) report th...

journal_title：Molecular cell

authors： Di Conza G,Tsai CH,Ho PC

更新日期：2019-10-03 00:00:00

abstract：:Genes are transcribed in a discontinuous pattern referred to as RNA bursting, but the mechanisms regulating this process are unclear. Although many physiological signals, including glucocorticoid hormones, are pulsatile, the effects of transient stimulation on bursting are unknown. Here we characterize RNA synthesis f...

journal_title：Molecular cell

authors： Stavreva DA,Garcia DA,Fettweis G,Gudla PR,Zaki GF,Soni V,McGowan A,Williams G,Huynh A,Palangat M,Schiltz RL,Johnson TA,Presman DM,Ferguson ML,Pegoraro G,Upadhyaya A,Hager GL

更新日期：2019-09-19 00:00:00

abstract：:Despite the relevance of Argonaute proteins in RNA silencing, little is known about the structural steps of small RNA loading to form RNA-induced silencing complexes (RISCs). We report the 1.9 Å crystal structure of human Argonaute4 with guide RNA. Comparison with the previously determined apo structure of Neurospora ...

journal_title：Molecular cell

authors： Park MS,Araya-Secchi R,Brackbill JA,Phan HD,Kehling AC,Abd El-Wahab EW,Dayeh DM,Sotomayor M,Nakanishi K

更新日期：2019-08-22 00:00:00

abstract：:YAP/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as...

journal_title：Molecular cell

authors： Zhu C,Li L,Zhang Z,Bi M,Wang H,Su W,Hernandez K,Liu P,Chen J,Chen M,Huang TH,Chen L,Liu Z

更新日期：2019-08-22 00:00:00

abstract：:HAT1 is an essential gene in mammals that acetylates newly synthesized histone H4 and is involved in chromatin assembly and genome maintenance. In this issue of Molecular Cell, Gruber et al. (2019) show that HAT1 binds to and stimulates H4 gene expression in a growth-factor- and glucose-dependent manner. ...

journal_title：Molecular cell

authors： Denu JM

更新日期：2019-08-22 00:00:00

abstract：:In two recent publications in Molecular Cell,Boulias et al. (2019) and Sendinc et al. (2019) use complementary approaches to map m6Am modification sites transcriptome-wide and demonstrate that m6Am can repress translation while increasing the stability of a subset of low-abundance transcripts. ...

journal_title：Molecular cell

authors： Doxtader KA,Nam Y

更新日期：2019-08-08 00:00:00

abstract：:The structural diversity of glycans on cells-the glycome-is vast and complex to decipher. Glycan arrays display oligosaccharides and are used to report glycan hapten binding epitopes. Glycan arrays are limited resources and present saccharides without the context of other glycans and glycoconjugates. We used maps of g...

journal_title：Molecular cell

authors： Narimatsu Y,Joshi HJ,Nason R,Van Coillie J,Karlsson R,Sun L,Ye Z,Chen YH,Schjoldager KT,Steentoft C,Furukawa S,Bensing BA,Sullam PM,Thompson AJ,Paulson JC,Büll C,Adema GJ,Mandel U,Hansen L,Bennett EP,Varki A,Vak

更新日期：2019-07-25 00:00:00

abstract：:Regulatory sequences or erroneous incorporations during DNA transcription cause RNA polymerase backtracking and inactivation in all kingdoms of life. Reactivation requires RNA transcript cleavage. Essential transcription factors (GreA and GreB, or TFIIS) accelerate this reaction. We report four cryo-EM reconstructions...

journal_title：Molecular cell

authors： Abdelkareem M,Saint-André C,Takacs M,Papai G,Crucifix C,Guo X,Ortiz J,Weixlbaumer A

更新日期：2019-07-25 00:00:00

abstract：:2'3'-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral stimulator of interferon genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, elicitin...

journal_title：Molecular cell

authors： Ritchie C,Cordova AF,Hess GT,Bassik MC,Li L

更新日期：2019-07-25 00:00:00

abstract：:Nonsense-mediated decay (NMD) is a surveillance system that degrades mRNAs containing a premature termination codon (PTC) and plays important roles in protein homeostasis and disease. The efficiency of NMD is variable, impacting the clinical outcome of genetic mutations. However, limited resolution of bulk analyses ha...

journal_title：Molecular cell

authors： Hoek TA,Khuperkar D,Lindeboom RGH,Sonneveld S,Verhagen BMP,Boersma S,Vermeulen M,Tanenbaum ME

更新日期：2019-07-25 00:00:00

abstract：:Multi-subunit SMC ATPases control chromosome superstructure and DNA topology, presumably by DNA translocation and loop extrusion. Chromosomal DNA is entrapped within the tripartite SMCkleisin ring. Juxtaposed SMC heads ("J heads") or engaged SMC heads ("E heads") split the SMCkleisin ring into "S" and "K" sub-compartm...

journal_title：Molecular cell

authors： Vazquez Nunez R,Ruiz Avila LB,Gruber S

更新日期：2019-07-25 00:00:00

abstract：:The essential histone H3 lysine 79 methyltransferase Dot1L regulates transcription and genomic stability and is deregulated in leukemia. The activity of Dot1L is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120Ub); however, the detailed mechanism is not understood. We report cryo-EM structures o...

journal_title：Molecular cell

authors： Valencia-Sánchez MI,De Ioannes P,Wang M,Vasilyev N,Chen R,Nudler E,Armache JP,Armache KJ

更新日期：2019-06-06 00:00:00

abstract：:Nucleotide-binding site leucine-rich repeat (NLR) receptors perceive pathogen effectors and trigger plant immunity. However, the mechanisms underlying NLR-triggered defense responses remain obscure. The recently discovered Pigm locus in rice encodes a cluster of NLRs, including PigmR, which confers broad-spectrum resi...

journal_title：Molecular cell

authors： Zhai K,Deng Y,Liang D,Tang J,Liu J,Yan B,Yin X,Lin H,Chen F,Yang D,Xie Z,Liu JY,Li Q,Zhang L,He Z

更新日期：2019-06-06 00:00:00

abstract：:Cryo-EM structures of Dot1L in complex with a ubiquitinated nucleosome provide the long-sought-after molecular mechanism of Dot1L-mediated methylation of lysine 79 in histone H3 and explain crosstalk with histone H2B ubiquitination. ...

journal_title：Molecular cell

authors： Zhang Y,Kutateladze TG

更新日期：2019-06-06 00:00:00

abstract：:The activity of the tumor suppressor p53 has to be timed and balanced closely to prevent untimely induction of cell death. The stability of p53 depends on the ubiquitin ligase Mdm2 but also on Hsp70 and Hsp90 chaperones that interact with its DNA binding domain (DBD). Using hydrogen exchange mass spectrometry and bioc...

journal_title：Molecular cell

authors： Boysen M,Kityk R,Mayer MP

更新日期：2019-05-16 00:00:00

abstract：:RNA flow between organisms has been documented within and among different kingdoms of life. Recently, we demonstrated horizontal RNA transfer between honeybees involving secretion and ingestion of worker and royal jellies. However, how the jelly facilitates transfer of RNA is still unknown. Here, we show that worker a...

journal_title：Molecular cell

authors： Maori E,Navarro IC,Boncristiani H,Seilly DJ,Rudolph KLM,Sapetschnig A,Lin CC,Ladbury JE,Evans JD,Heeney JL,Miska EA

更新日期：2019-05-02 00:00:00

abstract：:The convergence of two DNA replication forks creates unique problems during DNA replication termination. In E. coli and SV40, the release of torsional strain by type II topoisomerases is critical for converging replisomes to complete DNA synthesis, but the pathways that mediate fork convergence in eukaryotes are unkno...

journal_title：Molecular cell

authors： Deegan TD,Baxter J,Ortiz Bazán MÁ,Yeeles JTP,Labib KPM

更新日期：2019-04-18 00:00:00

abstract：:The diversity of mRNA lifetimes in bacterial cells is difficult to reconcile with the relaxed cleavage site specificity of RNase E, the endonuclease most important for governing mRNA degradation. This enzyme has generally been thought to locate cleavage sites by searching freely in three dimensions. However, our resul...

journal_title：Molecular cell

authors： Richards J,Belasco JG

更新日期：2019-04-18 00:00:00

abstract：:The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326-380 of p62 directly interact with the C-termina...

journal_title：Molecular cell

authors： Turco E,Witt M,Abert C,Bock-Bierbaum T,Su MY,Trapannone R,Sztacho M,Danieli A,Shi X,Zaffagnini G,Gamper A,Schuschnig M,Fracchiolla D,Bernklau D,Romanov J,Hartl M,Hurley JH,Daumke O,Martens S

更新日期：2019-04-18 00:00:00

abstract：:During X-inactivation, Xist RNA spreads along an entire chromosome to establish silencing. However, the mechanism and functional RNA elements involved in spreading remain undefined. By performing a comprehensive endogenous Xist deletion screen, we identify Repeat B as crucial for spreading Xist and maintaining Polycom...

journal_title：Molecular cell

authors： Colognori D,Sunwoo H,Kriz AJ,Wang CY,Lee JT

更新日期：2019-04-04 00:00:00

abstract：:Cardozo Gizzi et al. (2019) develop a new sequential imaging methodology (Hi-M) for observing chromosome structure in the Drosophila blastoderm and find that topological domains in single nuclei change in response to transcriptional activation. ...

journal_title：Molecular cell

authors： Larson DR

更新日期：2019-04-04 00:00:00

abstract：:BRCA1 functions at two distinct steps during homologous recombination (HR). Initially, it promotes DNA end resection, and subsequently it recruits the PALB2 and BRCA2 mediator complex, which stabilizes RAD51-DNA nucleoprotein filaments. Loss of 53BP1 rescues the HR defect in BRCA1-deficient cells by increasing resecti...

journal_title：Molecular cell

authors： Zong D,Adam S,Wang Y,Sasanuma H,Callén E,Murga M,Day A,Kruhlak MJ,Wong N,Munro M,Ray Chaudhuri A,Karim B,Xia B,Takeda S,Johnson N,Durocher D,Nussenzweig A

更新日期：2019-03-21 00:00:00

abstract：:The MHC class I antigen presentation system enables T cell immunosurveillance of cancers and viruses. A substantial fraction of the immunopeptidome derives from rapidly degraded nascent polypeptides (DRiPs). By knocking down each of the 80 ribosomal proteins, we identified proteins that modulate peptide generation wit...

journal_title：Molecular cell

authors： Wei J,Kishton RJ,Angel M,Conn CS,Dalla-Venezia N,Marcel V,Vincent A,Catez F,Ferré S,Ayadi L,Marchand V,Dersh D,Gibbs JS,Ivanov IP,Fridlyand N,Couté Y,Diaz JJ,Qian SB,Staudt LM,Restifo NP,Yewdell JW

更新日期：2019-03-21 00:00:00

abstract：:In this issue of Molecular Cell, Lu et al. (2019) analyze the role of the length and sequence complexity of the RNA polymerase II unstructured C-terminal domain in animal viability, development, and the dynamics of RNA polymerase II in vivo. ...

journal_title：Molecular cell

authors： Isaac RS,Churchman LS

更新日期：2019-03-21 00:00:00

abstract：:Wu et al. (2019) establish that the active zone proteins RIM and RIM-BP undergo liquid-liquid phase separation to tether Ca2+ channels. This important finding sets a new framework to study assembly and function of the presynaptic nerve terminal. ...

journal_title：Molecular cell

authors： Emperador-Melero J,Kaeser PS

更新日期：2019-03-07 00:00:00

abstract：:In Parkinson's disease (PD), α-synuclein (αS) pathologically impacts the brain, a highly lipid-rich organ. We investigated how alterations in αS or lipid/fatty acid homeostasis affect each other. Lipidomic profiling of human αS-expressing yeast revealed increases in oleic acid (OA, 18:1), diglycerides, and triglycerid...

journal_title：Molecular cell

authors： Fanning S,Haque A,Imberdis T,Baru V,Barrasa MI,Nuber S,Termine D,Ramalingam N,Ho GPH,Noble T,Sandoe J,Lou Y,Landgraf D,Freyzon Y,Newby G,Soldner F,Terry-Kantor E,Kim TE,Hofbauer HF,Becuwe M,Jaenisch R,Pincus D,

更新日期：2019-03-07 00:00:00

abstract：:CRISPR-Cas immunity requires integration of short, foreign DNA fragments into the host genome at the CRISPR locus, a site consisting of alternating repeat sequences and foreign-derived spacers. In most CRISPR systems, the proteins Cas1 and Cas2 form the integration complex and are both essential for DNA acquisition. M...

journal_title：Molecular cell

authors： Wright AV,Wang JY,Burstein D,Harrington LB,Paez-Espino D,Kyrpides NC,Iavarone AT,Banfield JF,Doudna JA

更新日期：2019-02-21 00:00:00