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RNA driving the epigenetic bus
Wed, 02/01/2012 - 00:00RNA driving the epigenetic bus
The EMBO Journal 31, 515 (2012). doi:10.1038/emboj.2011.479
Author: John S Mattick
EMBO J313, 522–533 (2012); published online 23 December 2011For many years, it has been assumed that mammalian development is primarily controlled by transcription factors, but recent studies, including that reported by Ng et al (2012) in this issue, indicate that there is an additional massive hidden layer of regulatory RNAs that control the site specificity of chromatin-modifying complexes and other regulatory proteins involved in the control of embryological and neural differentiation.
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Rac1 gets fattier
Wed, 02/01/2012 - 00:00Rac1 gets fattier
The EMBO Journal 31, 517 (2012). doi:10.1038/emboj.2011.481
Authors: Frederick D Tsai & Mark R Philips
EMBO J313, 534–551 (2012); published online 9 December 2011Since its description more than two decades ago as a substrate for botulinum C3 exoenzyme (Didsbury et al, 1989), Rac1 has been one of the most studied small GTPases of the Ras superfamily. Interest in Rac1 exploded in 1992 when Ridley and Hall published their seminal work showing that Rac1 regulates the actin cytoskeleton to promote lamellipodia formation (Ridley et al, 1992). Since that report, >4350 studies have been published on Rac1 and seemingly every detail of its regulation and biological function has been dissected, including its post-translational modifications. It therefore comes as somewhat of a surprise when del Pozo and colleagues (Navarro-Lérida et al, 2012) report for the first time in this issue of The EMBO Journal that Rac1 can be palmitoylated and that acylation directs its location in plasma membrane microdomains and modulates its signalling output.
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A structural road map to unveil basal body composition and assembly
Wed, 02/01/2012 - 00:00A structural road map to unveil basal body composition and assembly
The EMBO Journal 31, 519 (2012). doi:10.1038/emboj.2011.474
Authors: Swadhin C Jana, Pedro Machado & Mónica Bettencourt-Dias
EMBO J313, 552–562 (2012); published online 13 December 2011The Basal Body (BB) acts as the template for the axoneme, the microtubule-based structure of cilia and flagella. Although several proteins were recently implicated in both centriole and BB assembly and function, their molecular mechanisms are still poorly characterized. In this issue of The EMBO journal, Li and coworkers describe for the first time the near-native structure of the BB at 33 Å resolution obtained by Cryo-Electron Microscopy analysis of wild-type (WT) isolated Chlamydomonas BBs. They identified several uncharacterized non-tubulin structures and variations along the length of the BB, which likely reflect the binding and function of numerous macromolecular complexes. These complexes are expected to define BB intrinsic properties, such as its characteristic structure and stability. Similarly to the high-resolution structures of ribosome and nuclear pore complexes, this study will undoubtedly contribute towards the future analysis of centriole and BB biogenesis, maintenance and function.
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The nuclear receptor signalling scaffold: insights from full-length structures
Wed, 01/18/2012 - 00:00The nuclear receptor signalling scaffold: insights from full-length structures
The EMBO Journal 31, 251 (2012). doi:10.1038/emboj.2011.475
Authors: Jerome C Nwachukwu & Kendall W Nettles
EMBO J312, 291–300 (2012); published online 16 December 2011Nuclear receptors (NRs) can be conceptualized as highly dynamic scaffold proteins, where binding of ligand, DNA or transcriptional coregulator proteins can allosterically change the scaffold structure and direct changes in subsequent binding events. In this issue of The EMBO Journal, Orlov et al present the first cryo-EM structure of a NR complex, a technically challenging feat for the 100-kDa complex of the heterodimer of the vitamin D receptor (VDR), Retinoid X receptor (RXR) and their cognate DNA response element. VDR is one of the few NRs for which the hinge between the ligand-binding domain (LBD) and DNA-binding domain is an extended helix, which enforced a bend in VDR/RXR to an L-shaped architecture. The hinge domain is thus a key regulator of the relative orientation of the LBDs to the DNA, which will impact how transcriptional coregulator complexes are oriented towards the chromatin. It further suggests that the positioning of the hinge may serve as a conduit of structural information, determining how specific DNA sequences can modulate activity in the LBDs.
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Ubiquitin-mediated regulation of RhoGTPase signalling: IAPs and HACE1 enter the fray
Wed, 01/04/2012 - 00:00Ubiquitin-mediated regulation of RhoGTPase signalling: IAPs and HACE1 enter the fray
The EMBO Journal 31, 1 (2012). doi:10.1038/emboj.2011.452
Authors: Mariam Orme, Katiuscia Bianchi & Pascal Meier
Activation of members of the Rho-like family of guanosine triphosphatases GTPases (RhoGTPases) controls diverse physiological processes and is frequently found in cancer, contributing to tumour malignancy, cancer cell migration, invasion and metastasis. While the regulation of nucleotide binding to RhoGTPases is well understood, little is currently known regarding the molecular mechanisms through which RhoGTPase signalling is regulated by ubiquitylation. Two reports in this issue of The EMBO Journal and Developmental Cell now identify inhibitor of apoptosis (IAP) proteins and HACE1 as E3 ubiquitin (Ub)-protein ligases for Rac1 regulating Rac1 levels and activity.
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Hen1 is required for oocyte development and piRNA stability in zebrafish
Wed, 01/04/2012 - 00:00Hen1 is required for oocyte development and piRNA stability in zebrafish
The EMBO Journal 31, 248 (2012). doi:10.1038/emboj.2011.462
Authors: Leonie M Kamminga, Maartje J Luteijn, Marjo J den Broeder, Stefan Redl, Lucas JT Kaaij, Elke F Roovers, Peter Ladurner, Eugene Berezikov & René F Ketting
Correspondence to: r.ketting@hubrecht.euCorrection to:The EMBO Journal (2010) 29, 3688–3700. doi:10.1038/emboj.2010.233Since the publication of this article, the authors have placed the deep sequencing data at GEO. The accession number is GSE33582.The authors apologize for
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Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors
Fri, 12/23/2011 - 00:00Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors
The EMBO Journal 31, 522 (2012). doi:10.1038/emboj.2011.459
Authors: Shi-Yan Ng, Rory Johnson & Lawrence W Stanton
Long non-coding RNAs (lncRNAs) are a numerous class of newly discovered genes in the human genome, which have been proposed to be key regulators of biological processes, including stem cell pluripotency and neurogenesis. However, at present very little functional characterization of lncRNAs in human differentiation
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Mechanism of nucleotide sensing in group II chaperonins
Fri, 12/23/2011 - 00:00Mechanism of nucleotide sensing in group II chaperonins
The EMBO Journal 31, 731 (2012). doi:10.1038/emboj.2011.468
Authors: Jose H Pereira, Corie Y Ralston, Nicholai R Douglas, Ramya Kumar, Tom Lopez, Ryan P McAndrew, Kelly M Knee, Jonathan A King, Judith Frydman & Paul D Adams
Group II chaperonins mediate protein folding in an ATP-dependent manner in eukaryotes and archaea. The binding of ATP and subsequent hydrolysis promotes the closure of the multi-subunit rings where protein folding occurs. The mechanism by which local changes in the nucleotide-binding site are communicated between
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On epigenetics and epistasis: hybrids and their non-additive interactions
Fri, 12/23/2011 - 00:00On epigenetics and epistasis: hybrids and their non-additive interactions
The EMBO Journal 31, 249 (2012). doi:10.1038/emboj.2011.473
Authors: Lisa M Smith & Detlef Weigel
EMBO J312, 257–266 (2012); published online 16 December 2011Hybrid seeds have been a key component of greatly increasing the yield of many important crops, foremost of maize. If the parents are properly chosen, non-additive interactions between diverged genomes can lead to strongly superior performance of the F1 progeny, known as heterosis. While many different explanations have been advanced, a consensus for the causes of genome-wide positive epistasis in hybrids has not emerged. In this issue of The EMBO Journal, Shivaprasad and colleagues describe a new mechanism that can account for heterosis often being a genome-wide phenomenon. These authors show that small RNA (sRNA) loci of tomato can exhibit transgressive activity, which can in turn lead to epigenetic and gene expression changes within hybrid progeny. This is particularly exciting because many sRNAs are produced from non-coding regions or transposable elements (TEs), which diverge more quickly than protein-coding genes and thus provide more opportunity for unexpected genetic interactions.
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Extracellular matrix players in metastatic niches
Fri, 12/16/2011 - 00:00Extracellular matrix players in metastatic niches
The EMBO Journal 31, 254 (2012). doi:10.1038/emboj.2011.469
Authors: Thordur Oskarsson & Joan Massagué
Nature4817379, 85–89 (2012); published online 07 December 2011Metastatic niches support the survival and fitness of disseminated tumour cells (DTCs) in otherwise inhospitable tissue environments. The components of metastatic niches have remained a matter of conjecture, but recent reports, including one in a current issue of Nature, point at the extracellular matrix (ECM) proteins periostin and tenascin C (TNC) as key metastatic niche molecules. By enhancing Wnt and Notch signalling in cancer cells, these proteins provide physical as well as signalling support for metastasis-initiating cells. These findings underscore the importance of the ECM environment in cancer and provide potential drug targets against metastasis.
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Extraordinary transgressive phenotypes of hybrid tomato are influenced by epigenetics and small silencing RNAs
Fri, 12/16/2011 - 00:00Extraordinary transgressive phenotypes of hybrid tomato are influenced by epigenetics and small silencing RNAs
The EMBO Journal 31, 257 (2012). doi:10.1038/emboj.2011.458
Authors: Padubidri V Shivaprasad, Ruth M Dunn, Bruno ACM Santos, Andrew Bassett & David C Baulcombe
Hybrid organisms may fail to develop, be sterile or they may be more vigorous than either of the parents. Examples of hybrid vigour or hybrid necrosis in the F1 are often not inherited stably in subsequent generations if they are associated with overdominance. There can
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Structure of the full human RXR/VDR nuclear receptor heterodimer complex with its DR3 target DNA
Fri, 12/16/2011 - 00:00Structure of the full human RXR/VDR nuclear receptor heterodimer complex with its DR3 target DNA
The EMBO Journal 31, 291 (2012). doi:10.1038/emboj.2011.445
Authors: Igor Orlov, Natacha Rochel, Dino Moras & Bruno P Klaholz
Transcription regulation by steroid hormones and other metabolites is mediated by nuclear receptors (NRs) such as the vitamin D and retinoid X receptors (VDR and RXR). Here, we present the cryo electron microscopy (cryo-EM) structure of the heterodimeric complex of the liganded human RXR and
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Human pluripotent stem cells decouple respiration from energy production
Wed, 12/14/2011 - 00:00Human pluripotent stem cells decouple respiration from energy production
The EMBO Journal 30, 4851 (2011). doi:10.1038/emboj.2011.436
Authors: Ng Shyh-Chang, Yuxiang Zheng, Jason W Locasale & Lewis C Cantley
EMBO J3024, 4860–4873 (2011); published online 15 November 2011Human pluripotent stem cells (hPSCs) rely heavily on glycolysis for energy metabolism, and because their mitochondria appear poorly developed, hPSCs have been assumed to be incapable of using oxidative phosphorylation (OxPhos). In this issue, Zhang et al (2011) demonstrate that hPSCs actually possess functional OxPhos machinery, but that the mitochondrial protein UCP2 decouples OxPhos from glycolysis. The study further suggests that regulation of glucose metabolism by UCP2 facilitates hPSC pluripotency and controls hPSC differentiation.
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Building a double hexamer of DNA helicase at eukaryotic replication origins
Wed, 12/14/2011 - 00:00Building a double hexamer of DNA helicase at eukaryotic replication origins
The EMBO Journal 30, 4853 (2011). doi:10.1038/emboj.2011.437
Author: Karim Labib
EMBO J3024, 4885–4896 (2011); published online 1 November 2011The Mcm2-7 complex, the catalytic core of the eukaryotic replicative DNA helicase, undergoes a complex series of transformations at origins of DNA replication. During G1 phase, it is loaded around double-strand DNA at origins as an inactive double hexamer, which is subsequently remodelled in situ to activate the helicase during S phase. Work in this issue of The EMBO Journal sheds light on the role of the Cdt1 protein in generating Mcm2-7 double hexamers during the loading reaction.
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Rotate into shape: MreB and bacterial morphogenesis
Wed, 12/14/2011 - 00:00Rotate into shape: MreB and bacterial morphogenesis
The EMBO Journal 30, 4856 (2011). doi:10.1038/emboj.2011.430
Authors: Sven van Teeffelen & Zemer Gitai
EMBO J3024, 4931–4941 (2011); published online 30 September 2011MreB, the bacterial actin homologue, plays a vital role in determining cell shape, but the mechanisms by which it actually functions have remained largely mysterious. Recent studies now shed new light on MreB, demonstrating that it associates with many cell-wall synthesis enzymes, including a newly identified family of proteins that mediate teichoic acid synthesis in Gram-positive bacteria. Furthermore, MreB filaments dynamically rotate around the cell circumference in a manner dependent on the cell-wall assembly machinery. Thus, MreB may function to spatially organize the enzymatic activities required for proper bacterial growth (see Figure 1).
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miR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stress
Wed, 12/14/2011 - 00:00miR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stress
The EMBO Journal 30, 5021 (2011). doi:10.1038/emboj.2011.463
Authors: Jiening Xiao, Huixian Lin, Xiaobin Luo, Xiaoyan Luo & Zhiguo Wang
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Extracellular heat shock protein-90α: linking hypoxia to skin cell motility and wound healing
Wed, 12/14/2011 - 00:00Extracellular heat shock protein-90α: linking hypoxia to skin cell motility and wound healing
The EMBO Journal 30, 5022 (2011). doi:10.1038/emboj.2011.420
Authors: Wei Li, Yong Li, Shengxi Guan, Jianhua Fan, Chieh-Fang Cheng, Alexandra M Bright, Cindi Chinn, Mei Chen & David T Woodley
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Three-dimensional structure of basal body triplet revealed by electron cryo-tomography
Tue, 12/13/2011 - 00:00Three-dimensional structure of basal body triplet revealed by electron cryo-tomography
The EMBO Journal 31, 552 (2012). doi:10.1038/emboj.2011.460
Authors: Sam Li, Jose-Jesus Fernandez, Wallace F Marshall & David A Agard
Basal bodies and centrioles play central roles in microtubule (MT)-organizing centres within many eukaryotes. They share a barrel-shaped cylindrical structure composed of nine MT triplet blades. Here, we report the structure of the basal body triplet at 33 Å resolution obtained by electron cryo-tomography and
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A palmitoylation switch mechanism regulates Rac1 function and membrane organization
Fri, 12/09/2011 - 00:00A palmitoylation switch mechanism regulates Rac1 function and membrane organization
The EMBO Journal 31, 534 (2012). doi:10.1038/emboj.2011.446
Authors: Inmaculada Navarro-Lérida, Sara Sánchez-Perales, María Calvo, Carles Rentero, Yi Zheng, Carlos Enrich & Miguel A Del Pozo
The small GTPase Rac1 plays important roles in many processes, including cytoskeletal reorganization, cell migration, cell-cycle progression and gene expression. The initiation of Rac1 signalling requires at least two mechanisms: GTP loading via the guanosine triphosphate (GTP)/guanosine diphosphate (GDP) cycle, and targeting to cholesterol-rich liquid-ordered
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Endocytosis and intracellular trafficking contribute to necrotic neurodegeneration in C. elegans
Fri, 12/09/2011 - 00:00Endocytosis and intracellular trafficking contribute to necrotic neurodegeneration in C. elegans
The EMBO Journal 31, 654 (2012). doi:10.1038/emboj.2011.447
Authors: Kostoula Troulinaki & Nektarios Tavernarakis
Unlike apoptosis, necrotic cell death is characterized by marked loss of plasma membrane integrity. Leakage of cytoplasmic material to the extracellular space contributes to cell demise, and is the cause of acute inflammatory responses, which typically accompany necrosis. The mechanisms underlying plasma membrane damage during
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