Molecular biology

  • Article |

    PADI4 is an enzyme that converts arginine residues to citrulline. Here, Tanikawa and colleagues show that, in response to DNA damage, histone H4 and Lamin C are citrullinated in a p53 and PADI4-dependent manner andPadi4-dependent manner and Padi4 null mice are resistant to radiation-induced apoptosis in the thymus.

    • Chizu Tanikawa
    • , Martha Espinosa
    •  & Koichi Matsuda
  • Article
    | Open Access

    A systematic approach for identifying the genes responsible for the regulation of spindle orientation in mammals has been lacking. Now, Matsumuraet al. perform a kinase-targeting RNAi screen and identify ABL1, which through the direct phosphorylation of NuMa, is a novel regulator of spindle orientation.

    • Shigeru Matsumura
    • , Mayumi Hamasaki
    •  & Fumiko Toyoshima
  • Article
    | Open Access

    The super elongation complex, which is involved in transcriptional elongation, contains the Eleven-nineteen Lysine-rich Leukemia protein (ELL). In this study, ELL is shown to stabilize RNA polymerase II prior to recruitment into the super elongation complex, suggesting ELL has a role in early transcription elongation.

    • Jung S. Byun
    • , Temesgen D. Fufa
    •  & Kevin Gardner
  • Article
    | Open Access

    Albumin transport proteins circulate in the blood and are protected from degradation by interaction with the neonatal Fc receptor. Andersenet al. investigate the albumin binding site of the neonatal Fc receptor and find pH sensitive ionic networks at the binding interface.

    • Jan Terje Andersen
    • , Bjørn Dalhus
    •  & Inger Sandlie
  • Article
    | Open Access

    The tumour suppressor BRCA1 is mutated in familial breast and ovarian cancer. Now, Shuklaet al.demonstrate that mice lacking BRCA1 in cardiomyocytes are more sensitive to ischaemia than control mice, and that BRCA1 is elevated in human tissues exposed to ischaemia, suggesting a cardioprotective role for BRCA1.

    • Praphulla C. Shukla
    • , Krishna K. Singh
    •  & Subodh Verma
  • Article |

    The 30S ribosomal subunit ofEscherichia coliinhibits the RNA-degrading enzyme Ribonuclease T2. Using mutational studies and hybrid ribosomes, Kitahara and Miyazaki show that helix 41 of the 30S ribosomal subunit blocks the enzyme activity, suggesting that helix 41 is required for preventing RNase T2 toxicity.

    • Kei Kitahara
    •  & Kentaro Miyazaki
  • Article |

    Cell fusion is involved in many different cellular processes including the fusion of trophoblast cells in the placenta. Matsuuraet al. identify a role for the β-catenin signalling pathway in the regulation of the transcription factor GCM1 and therefore the fusion of syncytiotrophoblast cells.

    • Ken Matsuura
    • , Takafumi Jigami
    •  & Tetsu Akiyama
  • Article |

    The microRNA miR-137 is enriched in the brain of mice and induces the differentiation of adult neural stem cells. Now, Sun and colleagues report that miR-137 negatively regulates proliferation of neurons in embryonic mice and that TLX and LSD1 cooperate to negatively regulate miR-137 expression, blocking premature differentiation.

    • GuoQiang Sun
    • , Peng Ye
    •  & Yanhong Shi
  • Article
    | Open Access

    MicroRNAs bind to the 3′-untranslated region of genes to regulate expression. In this study, an RNA-binding protein, RMB38, is shown to selectively regulate the access of some microRNAs to their targets, and control the expression of some p53 target genes.

    • Nicolas Léveillé
    • , Ran Elkon
    •  & Reuven Agami
  • Article |

    The Golgi membrane is fragmented during mitosis and is subsequently fused following cell division and this process is known to be controlled by ubiquitination. In this study, the ubiquitin ligase HACE1 is shown to be targeted to the Golgi membrane and is required for fusion after the completion of mitosis.

    • Danming Tang
    • , Yi Xiang
    •  & Yanzhuang Wang
  • Article
    | Open Access

    What controls the binding partner selection of the target of rapamycin protein, TOR, is unknown. Using theCaenorhabditis elegans tail as a model, Nukazuka et al. determine that signals of semaphorin through plexin control the binding partner selection of TOR and are required for the correct organization of rays in the tail.

    • Akira Nukazuka
    • , Shusaku Tamaki
    •  & Shin Takagi
  • Article |

    Cellular senescence is characterized by the cessation of cell growth and the expression of the p16 protein. In this study, inhibition or loss of p300, a histone acetyltransferase, is shown to result in senescence that occurs independently of p16 and is associated with histone hypoacetylation and altered replication timing.

    • Alexandre Prieur
    • , Emilie Besnard
    •  & Jean-Marc Lemaitre
  • Article |

    Transforming growth factor-β blocks the activation of pro-inflammatory cytokines, in part by the degradation of Myd88. This study shows that smad ubiquitin regulator proteins are shown to mediate the destruction of Myd8 and are therefore required for the anti-inflammatory effects of transforming growth factor-β.

    • Youn Sook Lee
    • , Jin Seok Park
    •  & Seok Hee Park
  • Article
    | Open Access

    The appearance of a new intron that splits an exon without disrupting the corresponding peptide sequence is a rare event in vertebrate genomes. Hellstenet al.demonstrate that, under certain circumstances, a functional intron can be produced in a single step by segmental genomic duplication.

    • Uffe Hellsten
    • , Julie L. Aspden
    •  & Daniel S. Rokhsar
  • Article |

    Chromatin is rendered silent by epigenetic marks when in proximity to telomeres, and, in yeast, this effect requires the histone-modifying enzyme Sir2. In this study, the human Sir2 family member SIRT6 is shown to modulate the telomere position effect in human cells.

    • Ruth I. Tennen
    • , Dennis J. Bua
    •  & Katrin F. Chua
  • Article
    | Open Access

    RNA editing is important in regulating neuronal excitability, and a specific editing event has been shown to alter the permeation pathway of voltage-gate potassium channels. Gonzalezet al.find that the tip of the channel's inactivation gate makes a direct hydrophobic interaction with the edited position.

    • Carlos Gonzalez
    • , Angelica Lopez-Rodriguez
    •  & Miguel Holmgren
  • Article
    | Open Access

    The chronic disease schistosomiasis is caused by the blood flukeSchistosoma mansoni. By studying DNA modifications throughout the lifecycle of the pathogen, the authors identify DNA methylation as a factor in egg development and suggest that the epigenetic machinery responsible may be a therapeutic target.

    • Kathrin K. Geyer
    • , Carlos M. Rodríguez López
    •  & Karl F. Hoffmann
  • Article |

    MITF is a transcription factor required for melanocyte development, which is activated in some melanomas. Zhao and colleagues show that USP13 removes ubiquitin from MITF, stabilizes MITF protein levels and enhances colony formation, suggesting that USP13 may be a therapeutic target in melanoma.

    • Xiansi Zhao
    • , Brian Fiske
    •  & David E Fisher
  • Article
    | Open Access

    Polo-like kinase 1 is a key regulator of mitosis and is a candidate for drug development to treat cancer. Here, reduced expression of polo-like kinase 1 in adult mice has a minor impact on animal physiology, suggesting that polo-like kinase 1 inhibitors may be useful in the killing of tumour cells while sparing normal cells.

    • Monika Raab
    • , Sven Kappel
    •  & Klaus Strebhardt
  • Article
    | Open Access

    Posttranslational modification of proteins by small ubiquitin-related modifier is a response to stress signalling in plants. Here, theArabdiposisprotein SIZ1 is shown to cause SUMOylation of nitrate reductases 1 and 2 and to increase their activity, suggesting that SIZ1 controls nitrate uptake via SUMOylation.

    • Bong Soo Park
    • , Jong Tae Song
    •  & Hak Soo Seo
  • Article |

    Mutations in the DNA helicaseBLM cause Bloom syndrome, which is characterized by slow replication fork progression and genetic instability. Here, cells lacking BLMare shown to have a defect in cytidine deaminase, which alters the pyrimidine pool and results in replication fork progression with altered velocity.

    • Pauline Chabosseau
    • , Géraldine Buhagiar-Labarchède
    •  & Mounira Amor-Guéret
  • Article
    | Open Access

    There is debate about the structural organization of the yeast centromeric nucleosome and the role of the nonhistone protein Scm3 in its assembly. Dechassaet al.find that yeast centromeric nucleosomes organize DNA in a left-handed superhelix, and show that Scm3 is a specific nucleosome assembly factor.

    • Mekonnen Lemma Dechassa
    • , Katharina Wyns
    •  & Karolin Luger
  • Article
    | Open Access

    ADAR enzymes edit double-stranded RNA, converting adenosines to inosines, and are essential for neuronal function. Eggingtonet al. quantify edit sites in RNA using a Sanger sequencing protocol and use the resulting data to develop algorithms to predict RNA edit sites.

    • Julie M. Eggington
    • , Tom Greene
    •  & Brenda L. Bass
  • Article
    | Open Access

    IKK kinases activate nuclear factor-κB, and the activated form of this transcription factor is found in endothelial cells in diseased tissue. In this study, mice lacking IKKβ in the endothelium are generated, and it is shown that defects in endothelial cell function are both IKK kinase activity dependent and independent.

    • Noboru Ashida
    • , Sucharita SenBanerjee
    •  & Anthony Rosenzweig
  • Article
    | Open Access

    Duchenne muscular dystrophy is caused by a loss of thedystrophin gene, and control of dystrophin mRNA splicing could aid treatment of the disease. Nishida et al. show that a small molecule promotes skipping of exon 31 and increases production of a functional dystrophin protein in a patient.

    • Atsushi Nishida
    • , Naoyuki Kataoka
    •  & Masafumi Matsuo
  • Article
    | Open Access

    Saccharomycesyeasts can produce ethanol from sugars in the presence of oxygen. In this study, the authors demonstrate thatDekkera bruxellensis, a distantly related yeast, can also produce and consume ethanol due to the loss of a cis-regulatory element from the promoters of genes crucial for respiration.

    • Elżbieta Rozpędowska
    • , Linda Hellborg
    •  & Jure Piškur
  • Article
    | Open Access

    The study of prion diseases has been hampered as there is no method to distinguish newly formed abnormal prion protein conformers. Here, the authors describe a method to study newly formed abnormal prion protein and demonstrate that it is produced within 1 minute of cell exposure to prions.

    • R. Goold
    • , S. Rabbanian
    •  & S.J. Tabrizi
  • Article
    | Open Access

    Regulatory T cells are characterized by the expression of Foxp3, however, how the expression of this protein is controlled is unclear. Here, the authors show that the nuclear orphan receptor, Nr4a2, is a transcriptional activator of Foxp3, and suggest that it is required for the function of regulatory T cells.

    • Takashi Sekiya
    • , Ikkou Kashiwagi
    •  & Akihiko Yoshimura
  • Article
    | Open Access

    Plasmids are present in many bacteria and are often transferred between different species causing horizontal gene transfer. By comparing the sequences of 25 plasmid DNA backbones, the authors show that homologous recombination is prevalent in plasmids and that the plasmids have adapted to persist in different host bacteria.

    • Peter Norberg
    • , Maria Bergström
    •  & Malte Hermansson
  • Article |

    Phosphorylation of the microtubule-associated protein tau is associated with disease, but other post-translational modifications of tau are not well studied. Here, Cohenet al. study the acetylation of tau and suggest that this form of the protein may be associated with tauopathies.

    • Todd J. Cohen
    • , Jing L. Guo
    •  & Virginia M. Y. Lee
  • Article |

    Pronucleus DNA becomes demethylated during zygotic development. Here, the authors demonstrate that the reduction in 5-methylcytosine levels is accompanied by an increase in the presence of 5-hydroxymethylcytosine, and suggest that this has a role in developmental reprogramming.

    • Mark Wossidlo
    • , Toshinobu Nakamura
    •  & Jörn Walter
  • Article |

    Matrilocal and patrilocal populations are predicted to have greater genetic diversity in mitochondrial DNA and the Y-chromosome, respectively. Here, no difference in the diversity of the Y-chromosome was found in two such groups, suggesting that local diversity was caused by male gene flow in expanding populations.

    • Ellen Dröfn Gunnarsdóttir
    • , Madhusudan R. Nandineni
    •  & Mark Stoneking
  • Article
    | Open Access

    How one copy of the X chromosome is silenced in replicating female somatic cells is poorly understood. Here, the authors demonstrate that the inactive X chromosome is replicated before constitutive heterochromatin and that histone hypoacetylation has a role in controlling replication of the inactive X chromosome.

    • Corella S. Casas-Delucchi
    • , Alessandro Brero
    •  & M. Cristina Cardoso
  • Article
    | Open Access

    Hedgehog signalling gradients are required for proper wing formation inDrosophila, and Hedgehog is known to regulate the cubitus interruptus transcription factor. Here, the authors show that the COP9 signalosome has a critical role in translating a Hedgehog gradient into a cubitus interruptus gradient.

    • June-Tai Wu
    • , Wei-Hsiang Lin
    •  & Cheng-Ting Chien
  • Article
    | Open Access

    Post-translational modifications are important in regulating protein function and turnover, and Ufm1 is part of a recently identified protein modification system. In this study, the authors show that Uba5, a component of the Ufm1 system, is important for regulating haematopoiesis and the differentiation of erythroid cells.

    • Kanako Tatsumi
    • , Harumi Yamamoto-Mukai
    •  & Masaaki Komatsu
  • Article |

    Rad23 accompanies ubiquitinated substrates to the proteasome for destruction but manages to avoid degradation. In this study, Fishbainet that Rad23 escapes because it lacks an effective initiation region; therefore, the proteasome is unable to engage the protein and unfold it.

    • Susan Fishbain
    • , Sumit Prakash
    •  & Andreas Matouschek
  • Article |

    Uridines at the wobble position of transfer RNA anticodons are usually modified to allow efficient decoding of messenger RNA codons. In this study, ALKBH8 is shown to be a bifunctional transfer RNA modification enzyme required for the formation of a novel diastereomeric pair of modified wobble uridines.

    • Erwin van den Born
    • , Cathrine B. Vågbø
    •  & Pål Ø. Falnes
  • Article
    | Open Access

    The control of cell fate and apoptosis is a continuing challenge in synthetic biology. In this study, systems are developed in which an intracellularly expressed genome-encoded protein simultaneously achieves up- and downregulation of two distinct apoptosis pathways.

    • Hirohide Saito
    • , Yoshihiko Fujita
    •  & Tan Inoue