Nature Structural & Molecular Biology Contents: October 2012 Volume #19 pp 973 - 1037

TABLE OF CONTENTS October 2012 Volume 19, Issue 10 News and Views Research Highlights Articles Resources Technical Report Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement The Encyclopedia of DNA Elements 30 papers published simultaneously in Nature, Genome Research and Genome Biology. Access videos, Features and the collected research papers, and explore the thematic threads that run through them via the Nature ENCODE explorer or the NatureENCODE app. Produced with support from Illumina   News and Views Top Context is everything: activators can also repress   pp973 - 975 Richard Festenstein and Jackson P K Chan doi:10.1038/nsmb.2401 Maintenance of genome integrity, cell division and gene expression have all been shown to be regulated by the condensation of DNA into heterochromatin. In a study published in this issue, Bulut-Karslioglu et al. reveal a new heterochromatin function for transcription factors in a mammalian system. They show that instead of activating gene expression, in the context of heterochromatic repeats, specific transcription factors are necessary for the maintenance of transcriptional repression and heterochromatin. See also: Article by Bulut-Karslioglu et al. Two-step insertion at the SecY translocon   pp975 - 977 Soo Jung Kim and William R Skach doi:10.1038/nsmb.2402 SecY and Sec61 translocons mediate the orderly insertion of transmembrane segments into the lipid bilayer during membrane-protein biogenesis. Reporting in this issue, Ismail et al. now use a SecM-based molecular force sensor to show that the translocon exerts a pulling force on the nascent chain that is capable of mechanical action at two distinct stages of the insertion process. See also: Article by Ismail et al. Solving the mystery of procollagen chain selectivity   pp977 - 978 Neil J Bulleid doi:10.1038/nsmb.2397 The recently solved crystal structure of the procollagen C propeptide reveals the basis for chain selectivity as well as an unexpected asymmetry to this homotrimeric molecule. In addition, mapping disease-causing mutations to the structure demonstrates clear correlation between severity of disease and mutation location. See also: Article by Bourhis et al. Making the cut: intramembrane cleavage by a rhomboid protease promotes ERAD   pp979 - 981 Ethan J Greenblatt, James A Olzmann and Ron R Kopito doi:10.1038/nsmb.2398 Endoplasmic reticulum-associated degradation (ERAD) is a cellular protein quality-control process that disposes of proteasomal substrates from the early secretory pathway. Recent work shows that the endoplasmic reticulum-resident rhomboid protease RHBDL4 facilitates ERAD by recognizing and cleaving integral membrane substrates. The work indicates that intramembrane proteolysis may have a general role in the extraction of misfolded membrane proteins from the endoplasmic reticulum. Structural & Molecular Biology JOBS of the week Assistant Professor Structural Biology Brown University University Lectureship in Biochemistry, Structural Biology and Biophysics University of Oxford Postdoctoral Position in Membrane Protein Structural Biology with NMR Biozentrum Basel Postdoc In Structural Biology Institute of Organic Chemistry and Biochemistry AS CR More Science jobs from Structural & Molecular Biology EVENT 10th International Conference on Damage Assessment of Structures (DAMAS 2013) 8th-10th July 2013 Dublin, Ireland More science events from Research Highlights Top Branching regulation | Pulling recombination apart | Death control | Bent out of shape Articles Top Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly   pp983 - 990 Isabelle Barbosa, Nazmul Haque, Francesca Fiorini, Charlotte Barrandon, Catherine Tomasetto, Marco Blanchette and Hervé Le Hir doi:10.1038/nsmb.2380 The exon junction complex (EJC) links splicing to downstream events including mRNA localization, translation and stability. A combination of in vitro and in vivo approaches were used to identify the splicing factor CWC22 as a direct partner of EJC component eIF4AIII in flies and humans and to demonstrate its functions in preventing eIF4AIII binding to RNA and in escorting eIF4AIII to active spliceosomes before EJC assembly. Controlling synaptotagmin activity by electrostatic screening   pp991 - 997 Yongsoo Park, Javier M Hernandez, Geert van den Bogaart, Saheeb Ahmed, Matthew Holt, Dietmar Riedel and Reinhard Jahn doi:10.1038/nsmb.2375 Synaptotagmin promotes SNARE-mediated membrane fusion in a Ca2+-dependent manner, but the mechanism by which it acts is still unclear. In vitro studies have shown that synaptotagmin can make interactions with its own vesicle membrane, inhibiting its ability to stimulate fusion with target membranes. New data now suggest that ATP and other polybasic anions may have a role in directing synaptotagmin to its target membrane in vivo. Argonaute proteins couple chromatin silencing to alternative splicing   pp998 - 1004 Maya Ameyar-Zazoua, Christophe Rachez, Mouloud Souidi, Philippe Robin, Lauriane Fritsch, Robert Young, Nadya Morozova, Romain Fenouil, Nicolas Descostes, Jean-Christophe Andrau, Jacques Mathieu, Ali Hamiche, Slimane Ait-Si-Ali, Christian Muchardt, Eric Batsché and Annick Harel-Bellan doi:10.1038/nsmb.2373 The function of nuclear Argonaute proteins in somatic mammalian cells has remained elusive. A new study shows that chromatin-bound Argonaute-1 and Argonaute-2 associate with splicing factors and affect the deposition of histone marks, thereby facilitating spliceosome recruitment and modulating the RNA polymerase II elongation rate. This in turn favors inclusion of variant exons in the mature mRNA. The APOBEC3C crystal structure and the interface for HIV-1 Vif binding   pp1005 - 1010 Shingo Kitamura, Hirotaka Ode, Masaaki Nakashima, Mayumi Imahashi, Yuriko Naganawa, Teppei Kurosawa, Yoshiyuki Yokomaku, Takashi Yamane, Nobuhisa Watanabe, Atsuo Suzuki, Wataru Sugiura and Yasumasa Iwatani doi:10.1038/nsmb.2378 APOBEC3 (A3) proteins are cytidine deaminases that can restrict retroviral replication by causing hypermutation of the viral genome. The HIV-1 protein Vif counteracts the action of A3s by promoting their degradation. Now the crystal structure of A3C and homology models for A3F and A3DE, together with mutagenesis analyses, allow the identification of their interaction interface with Vif, which is different from a previously implicated region in A3G. Dxo1 is a new type of eukaryotic enzyme with both decapping and 5′-3′ exoribonuclease activity   pp1011 - 1017 Jeong Ho Chang, Xinfu Jiao, Kunitoshi Chiba, ChanSeok Oh, Charles E Martin, Megerditch Kiledjian and Liang Tong doi:10.1038/nsmb.2381 Rail1 is a component of the mRNA 5′-end quality-control mechanism in yeast. Structural, biochemical and functional studies of its homolog in Kluyveromyces lactis now reveal that the enzyme, dubbed Dxo1, has not only decapping but also 5′-3′ exonuclease activity, enabling it to single-handedly decap and degrade mRNAs from the 5′ end. A biphasic pulling force acts on transmembrane helices during translocon-mediated membrane integration   pp1018 - 1022 Nurzian Ismail, Rickard Hedman, Nina Schiller and Gunnar von Heijne doi:10.1038/nsmb.2376 Most membrane proteins are co-translationally inserted into the membrane with the aid of Sec-type translocons. Using so-called translation-arrest peptides derived from bacterial and mammalian proteins as natural force sensors, a new study now demonstrates how force is exerted on a nascent chain at two distinct points in a transmembrane helix during its transit through the translocon channel into the membrane. See also: News and Views by Kim & Skach A transcription factor–based mechanism for mouse heterochromatin formation   pp1023 - 1030 Aydan  Bulut-Karslioglu, Valentina Perrera, Manuela Scaranaro, Inti Alberto de la Rosa-Velazquez, Suzanne van de Nobelen, Nicholas Shukeir, Johannes Popow, Borbala Gerle, Susanne Opravil, Michaela Pagani, Simone Meidhof, Thomas Brabletz, Thomas Manke, Monika Lachner and Thomas Jenuwein doi:10.1038/nsmb.2382 The mechanisms that initiate heterochromatin formation and maintain its distinction from euchromatin have remained elusive. However, a new study reveals a pathway in which transcriptional repression of pericentric repeats by sequence-specific transcription factors is essential for the integrity of heterochromatin, thereby considerably expanding the role of transcription factors beyond euchromatic gene regulation. See also: News and Views by Festenstein & Chan Structural basis of fibrillar collagen trimerization and related genetic disorders   pp1031 - 1036 Jean-Marie Bourhis, Natacha Mariano, Yuguang Zhao, Karl Harlos, Jean-Yves Exposito, E Yvonne Jones, Catherine Moali, Nushin Aghajari and David J S Hulmes doi:10.1038/nsmb.2389 Procollagen, the precursor of collagen, contains a large C-terminal domain called COLFI that initiates homotrimerization and harbors mutations associated with different diseases. Now the crystal structure of the COLFI domain from human procollagen III is presented, revealing the mechanisms for specificity of trimer formation and the position of disease-related mutations. See also: News and Views by Bulleid Resources Top 5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary   pp1037 - 1043 Tarang Khare, Shraddha Pai, Karolis Koncevicius, Mrinal Pal, Edita Kriukiene, Zita Liutkeviciute, Manuel Irimia, Peixin Jia, Carolyn Ptak, Menghang Xia, Raymond Tice, Mamoru Tochigi, Solange Moréra, Anaies Nazarians, Denise Belsham, Albert H C Wong, Benjamin J Blencowe, Sun Chong Wang, Philipp Kapranov, Rafal Kustra, Viviane Labrie, Saulius Klimasauskas and Arturas Petronis doi:10.1038/nsmb.2372 The 5-hydroxymethylcytosine (5-hmC) nucleoside is abundant in the brain for unknown reasons. Genome-wide analysis of the distribution of 5-hmC versus 5-methylcytosine (5-mC) in human and mouse tissues now shows that 5-hmC is enriched in genes with synaptic functions. The differential distribution of 5-hmC versus 5-mC at exon-intron boundaries in both human and mouse tissues further suggests a possible role for 5-hmC in pre-mRNA splicing. Intronic splicing enhancers, cognate splicing factors and context-dependent regulation rules   pp1044 - 1052 Yang Wang, Meng Ma, Xinshu Xiao and Zefeng Wang doi:10.1038/nsmb.2377 A systematic, unbiased screen for general intronic splicing enhancers (ISEs) identified >100 ISEs that promote intron splicing but inhibit splicing in exons. Putative trans-factors for clusters of ISEs were identified, validated and were found to control ISE activity in a context-dependent manner. Altogether, the data provide a comprehensive picture of how ISEs function depending on their location and cognate trans-factors. Technical Report Top Spatial elucidation of motion in proteins by ensemble-based structure calculation using exact NOEs   pp1053 - 1057 Beat Vögeli, Sina Kazemi, Peter Güntert and Roland Riek doi:10.1038/nsmb.2355 NMR relaxation phenomena give insight into local protein motions, and understanding protein dynamics can aid in understanding protein function. Nuclear Overhauser enhancements (NOEs) have been traditionally used to determine protein structure by NMR, but a novel application using exact NOEs provides a structural ensemble that describes a protein's structure as well as its dynamics. Top Advertisement Nature.com presents Antibodypedia Finding the right antibody for the right application just got easier! 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