Volume 19 Issue 10, October 2012

Volume 19 Issue 10

Jenuwein and colleagues propose a transcription factor (TF)-based model for heterochromatin formation. On the cover, this model is illustrated by the Matterhorn of the Swiss Alps, which resembles the sharp TF peaks found at promoters. Les Droites of the Mont Blanc are reminiscent of reiterated TF binding sites within heterochromatin. Cover images provided by the Jenuwein laboratory. pp 1023–1030, News and Views p 973

News and Views

  • News & Views |

    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.

    • Richard Festenstein
    •  & Jackson P K Chan
  • News & Views |

    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.

    • Soo Jung Kim
    •  & William R Skach
  • News & Views |

    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.

    • Neil J Bulleid
  • News & Views |

    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.

    • Ethan J Greenblatt
    • , James A Olzmann
    •  & Ron R Kopito

Research Highlights


  • Article |

    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.

    • Isabelle Barbosa
    • , Nazmul Haque
    • , Francesca Fiorini
    • , Charlotte Barrandon
    • , Catherine Tomasetto
    • , Marco Blanchette
    •  & Hervé Le Hir
  • Article |

    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.

    • Yongsoo Park
    • , Javier M Hernandez
    • , Geert van den Bogaart
    • , Saheeb Ahmed
    • , Matthew Holt
    • , Dietmar Riedel
    •  & Reinhard Jahn
  • Article |

    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.

    • 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
    •  & Annick Harel-Bellan
  • Article |

    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.

    • Shingo Kitamura
    • , Hirotaka Ode
    • , Masaaki Nakashima
    • , Mayumi Imahashi
    • , Yuriko Naganawa
    • , Teppei Kurosawa
    • , Yoshiyuki Yokomaku
    • , Takashi Yamane
    • , Nobuhisa Watanabe
    • , Atsuo Suzuki
    • , Wataru Sugiura
    •  & Yasumasa Iwatani
  • Article |

    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.

    • Jeong Ho Chang
    • , Xinfu Jiao
    • , Kunitoshi Chiba
    • , ChanSeok Oh
    • , Charles E Martin
    • , Megerditch Kiledjian
    •  & Liang Tong
  • Article |

    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.

    • Nurzian Ismail
    • , Rickard Hedman
    • , Nina Schiller
    •  & Gunnar von Heijne
  • Article |

    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.

    • 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
    •  & Thomas Jenuwein
  • Article |

    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.

    • Jean-Marie Bourhis
    • , Natacha Mariano
    • , Yuguang Zhao
    • , Karl Harlos
    • , Jean-Yves Exposito
    • , E Yvonne Jones
    • , Catherine Moali
    • , Nushin Aghajari
    •  & David J S Hulmes


  • Resource |

    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.

    • 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
    •  & Arturas Petronis
  • Resource |

    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.

    • Yang Wang
    • , Meng Ma
    • , Xinshu Xiao
    •  & Zefeng Wang

Technical Report

  • Technical Report |

    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.

    • Beat Vögeli
    • , Sina Kazemi
    • , Peter Güntert
    •  & Roland Riek