Nature Structural & Molecular Biology Contents: August 2012 Volume #19 pp 737 - 852

TABLE OF CONTENTS August 2012 Volume 19, Issue 8 News and Views Research Highlights Articles Brief Communications Resources Advertisement WHET YOUR APP-ETITEâ€" Arteriosclerosis, Thrombosis, and Vascular Biology for the iPad®. Research that's critical to your profession is now brought to you on the iPad. Sample issue is available-click here to download the app for free today! Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Communications #4 in multidisciplinary sciences with first Impact Factor Nature Communications has joined Nature at the top of the multidisciplinary sciences category with its first impact factor of 7.396* Launched in April 2010, Nature Communications is a multidisciplinary online-only journal publishing high quality research across the natural sciences. *2011 Journal Citation Reports® (Thomson Reuters, 2012)   News and Views Top PICking apart Pol II initiation   pp737 - 738 Michael Carey doi:10.1038/nsmb.2349 The recent mapping and modeling of protein-protein interfaces between general transcription factors TFIIE, TFIIH and Pol II have provided new insights into TFIIH-mediated melting of the transcription start site to form an open Pol II preinitiation complex and the stabilization of the complex by TFIIE, leading to a new mechanistic model for open-complex formation. See also: Article by Grünberg et al. Writers and readers: deconvoluting the harmonic complexity of the histone code   pp739 - 740 Michael S Cosgrove doi:10.1038/nsmb.2350 The application of time-resolved NMR spectroscopy to histone phosphorylation dynamics reveals mechanistic hierarchies within the active sites of the enzymes that regulate chromatin, thereby shedding new light on the complexity of the histone code. See also: Article by Liokatis et al. Replication origins run (ultra) deep   pp740 - 742 David M Gilbert doi:10.1038/nsmb.2352 The search for the holy replicator has been revitalized through ultradeep sequencing of small RNA-primed single-stranded DNA. Saturation sequencing provides an explanation for the lack of overlap in prior data sets, suggests that frequency of origin usage but not site selection is developmentally regulated, and uncovers a complex four-stranded DNA structure associated with most origins. See also: Resource by Besnard et al. Research Highlights Entropy controls activity | The STING of viral fusion | Expanding the CTD code Structural & Molecular Biology JOBS of the week Structural Cellular Biology Postdoc Okinawa Institute of Science and Technology Graduate University Postdoc - Structural Biology Duke University Post-doc position in molecular spectroscopy University of Louisville International PhD Program Molecular Neurobiology (MolNeuro) Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch - Helmholtz Association Postdoctoral Researcher in Yeast Molecular Genetics NUI Galway Ireland More Science jobs from Structural & Molecular Biology EVENT X-Ray Methods in Structural Biology 15th - 30th Oct 2012 US More science events from Articles Top Proofreading of pre-40S ribosome maturation by a translation initiation factor and 60S subunits   pp744 - 753 Simon Lebaron, Claudia Schneider, Robert W van Nues, Agata Swiatkowska, Dietrich Walsh, Bettina Böttcher, Sander Granneman, Nicholas J Watkins and David Tollervey doi:10.1038/nsmb.2308 During the final stages of yeast ribosome synthesis, immature translation-incompetent pre-40S particles that contain 20S pre-rRNA are converted to the mature translation-competent subunits containing 18S rRNA. In vitro and in vivo data now demonstrate that processing of 20S pre-rRNA is stimulated by translation initiation factor Fun12, and that its interaction with 60S ribosomal subunits is required for efficient 20S pre-rRNA processing. Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F   pp754 - 759 Rajintha M Bandaranayake, Daniela Ungureanu, Yibing Shan, David E Shaw, Olli Silvennoinen and Stevan R Hubbard doi:10.1038/nsmb.2348 Human JAK2 tyrosine kinase mediates signaling through numerous cytokine receptors. The JAK2 JH2 pseudokinase domain negatively regulates the activity of the JH1 kinase domain. The structures of wild-type JH2 and of the dominant V617F mutant provide a solid foundation for discerning the mechanism of action of the JH2 domain in normal JAK signaling and in dysregulated signaling that causes disease. DGCR8 HITS-CLIP reveals novel functions for the Microprocessor   pp760 - 766 Sara Macias, Mireya Plass, Agata Stajuda, Gracjan Michlewski, Eduardo Eyras and Javier F Cáceres doi:10.1038/nsmb.2344 The Drosha–DGCR8, or Microprocessor, complex, is required for microRNA biogenesis. DGCR8 recognizes the RNA substrates, whereas Drosha functions as an endonuclease. High-throughput sequencing and cross-linking immunoprecipitation (HITS-CLIP) analyses reveal many other RNA targets of DGCR8 besides microRNAs, including snoRNAs, which are processed in a Drosha-independent manner, as well as long noncoding RNAs and mRNAs of protein-coding genes. The mechanism of patellamide macrocyclization revealed by the characterization of the PatG macrocyclase domain   pp767 - 772 Jesko Koehnke, Andrew Bent, Wael E Houssen, David Zollman, Falk Morawitz, Sally Shirran, Jeremie Vendome, Ada F Nneoyiegbe, Laurent Trembleau, Catherine H Botting, Margaret C M Smith, Marcel Jaspars and James H Naismith doi:10.1038/nsmb.2340 The subtilisin-like domain of PatG can catalyze the macrocyclization of linear peptide. The crystal structure of the PatG macrocyclase domain, along with mutagenesis and functional analyses, reveals how the enzyme recognizes its substrate and enforces macrocyclization over hydrolysis of the acyl-enzyme intermediate. This information is also used to engineer variants with altered specificity and enhanced catalytic activity. Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis   pp773 - 781 Anastassios Vourekas, Qi Zheng, Panagiotis Alexiou, Manolis Maragkakis, Yohei Kirino, Brian D Gregory and Zissimos Mourelatos doi:10.1038/nsmb.2347 Piwi proteins bind a class of small germline RNAs, called piRNAs, whose biogenesis and functions are largely unknown. High-throughput sequencing after cross-linking and immunoprecipitation (HITS-CLIP) analysis in combination with RNA sequencing to analyze the genome-wide RNA target repertoire of mouse Piwi (Miwi) proteins in testis uncovers the in vivo piRNA biogenesis pathway and demonstrates that Miwi binds spermiogenic RNAs directly without using piRNAs as guides. Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase   pp782 - 787 Luke A Yates, Sophie Fleurdépine, Olivia S Rissland, Luigi De Colibus, Karl Harlos, Chris J Norbury and Robert J C Gilbert doi:10.1038/nsmb.2329 The post-transcriptional addition of uridyl ribonucleotides by terminal uridyltransferases (TUTases) to the ′A ends of various cytoplasmic RNAs, including microRNAs, has been implicated in regulating their stability, biogenesis or activity. The crystal structure of Schizosaccharomyces pombe TUTase Cid1 in its apo form and bound to UTP provides insight into the enzyme's active site, UTP selectivity and RNA-binding mechanism. Architecture of the RNA polymerase II preinitiation complex and mechanism of ATP-dependent promoter opening   pp788 - 796 Sebastian Grünberg, Linda Warfield and Steven Hahn doi:10.1038/nsmb.2334 The general transcription factors TFIIE and TFIIH subunit Ssl2/XPB function in the transition of the preinitiation complex (PIC) to the open polymerase II (Pol II) complex. Efforts to localize TFIIE and Ssl2 in the yeast PIC now reveal crucial roles for the three TFIIE winged-helix domains and for Ssl2 in promoting DNA strand separation. See also: News and Views by Carey Stochastic expression dynamics of a transcription factor revealed by single-molecule noise analysis   pp797 - 802 Zach Hensel, Haidong Feng, Bo Han, Christine Hatem, Jin Wang and Jie Xiao doi:10.1038/nsmb.2336 How intrinsic stochasticity of gene expression is controlled is not well understood. A quantitative single-molecule analysis of transcription factor expression dynamics based on a new strategy (cotranslational activation by cleavage, or CoTrAC), sheds light on the mechanisms that cells use to control noise in gene regulatory networks. LEDGF (p75) promotes DNA-end resection and homologous recombination   pp803 - 810 Mads Daugaard, Annika Baude, Kasper Fugger, Lou Klitgaard Povlsen, Halfdan Beck, Claus Storgaard Sørensen, Nikolaj H T Petersen, Poul H B Sorensen, Claudia Lukas, Jiri Bartek, Jiri Lukas, Mikkel Rohde and Marja Jäättelä doi:10.1038/nsmb.2314 LEDGF (p75) is a chromatin-binding protein implicated in cancer, autoimmune disease and HIV-1 pathogenesis, but its cellular function was still unclear. Now LEDGF is found to have a role in the repair of DNA double-stranded breaks via homologous recombination, promoting end resection by CtIP. Cyclic AMP regulation of protein lysine acetylation in Mycobacterium tuberculosis    pp811 - 818 Ho Jun Lee, P Therese Lang, Sarah M Fortune, Christopher M Sassetti and Tom Alber doi:10.1038/nsmb.2318 In Mycobacterium tuberculosis, the activity of a protein lysine acetyltransferase (PAT) is allosterically regulated by cAMP binding to a domain fused to the catalytic domain. Now the crystal structures of the autoinhibited and cAMP-activated PAT, along with biochemical analysis, reveal how allosteric regulation between independent protein domains can evolve. Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events   pp819 - 823 Stamatios Liokatis, Alexandra Stützer, Simon J Elsässer, Francois-Xavier Theillet, Rebecca Klingberg, Barth van Rossum, Dirk Schwarzer, C David Allis, Wolfgang Fischle and Philipp Selenko doi:10.1038/nsmb.2310 Phosphorylation of residues in the N-terminal tail of histone H3 signals different biological outcomes. High-resolution NMR analyses now reveal a mechanistic hierarchy of H3 phosphorylation events, whereby phosphorylation of Ser10 impedes the phosphorylation of Thr6 and Thr11 by PKC and Chk1, respectively. Because both enzymes also target Ser10, this establishes an autoinhibitory feedback loop on H3 tails. See also: News and Views by Cosgrove The translin–TRAX complex (C3PO) is a ribonuclease in tRNA processing   pp824 - 830 Liande Li, Weifeng Gu, Chunyang Liang, Qinghua Liu, Craig C Mello and Yi Liu doi:10.1038/nsmb.2337 While the conserved translin–TRAX complex (also known as C3PO) functions as an endoribonuclease that promotes RNA interference (RNAi) in animal cells, new research shows that C3PO is not involved in RNAi in Neurospora crassa but instead functions as a ribonuclease that removes the 5′ pre-tRNA fragments after processing of pre-tRNAs by RNase P. This function may be conserved in mammals. Brief Communications Top 5-formylcytosine and 5-carboxylcytosine reduce the rate and substrate specificity of RNA polymerase II transcription   pp831 - 833 Matthew W Kellinger, Chun-Xiao Song, Jenny Chong, Xing-Yu Lu, Chuan He and Dong Wang doi:10.1038/nsmb.2346 A systematic in vitro analysis of five different forms of cytosine in mammalian and yeast RNA polymerase II (Pol II) transcription demonstrates that Pol II can read and distinguish subtle differences in modified cytosines and process them differently, suggesting a putative functional interplay between cytosine modification status and transcription. Functional characterization of an active Rag-like transposase    pp834 - 836 Cary G Hencken, Xianghong Li and Nancy L Craig doi:10.1038/nsmb.2338 The assembly of diverse immunoglobulin genes results in part from Rag protein–mediated DNA double-strand breaks at the edges of immunoglobulin gene segments, followed by the combinatorial reassembly of these segments. A transposase from the insect Helicoverpa zea is now shown to be active in vitro, and its breakage and joining activities resemble those of Rag, suggesting a common progenitor. Resources Top Unraveling cell type–specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs   pp837 - 844 Emilie Besnard, Amélie Babled, Laure Lapasset, Ollivier Milhavet, Hugues Parrinello, Christelle Dantec, Jean-Michel Marin and Jean-Marc Lemaitre doi:10.1038/nsmb.2339 How metazoans determine where to initiate DNA replication remains mysterious. Now deep sequencing of short nascent strands in different human cell types provides an extensive map of replication origins, identifying cell type–specific signatures and a putative consensus motif with the potential to form G-quadruplex structures. See also: News and Views by Gilbert Direct sequencing of Arabidopsis thaliana RNA reveals patterns of cleavage and polyadenylation   pp845 - 852 Alexander Sherstnev, Céline Duc, Christian Cole, Vasiliki Zacharaki, Csaba Hornyik, Fatih Ozsolak, Patrice M Milos, Geoffrey J Barton and Gordon G Simpson doi:10.1038/nsmb.2345 RNA 3′-end formation is thought to be crucial in controlling gene expression. Direct RNA sequencing was used to analyze the 3′ ends of Arabidopsis thaliana RNA in unprecedented detail, revealing extreme heterogeneity of RNA 3′ ends, patterns of cleavage and polyadenylation, and previously unrecognized noncoding RNAs. Top Advertisement Feel like your paper is lost in a sea of submissions? Scientific Reports publishes your research quickly and efficiently, and makes it freely available to the global scientific community. 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