Molecular biology

  • Article |

    The TREX complex and Nxf1 are involved in the export of mRNA from the nucleus but the precise molecular function of TREX is unclear. Here, the TREX components Aly and Thoc5 are shown to bind to Nxf1 resulting in a change in Nxf1 conformation that permits binding to mRNA and nuclear export.

    • Nicolas Viphakone
    • , Guillaume M. Hautbergue
    •  & Stuart A. Wilson
  • Article |

    The protein ataxia-telangiectasia mutated (ATM) detects DNA damage and can trigger cellular apoptosis, but how this process is regulated at the molecular level is unclear. Here, Chunget al. show that the transcription factor FOXO3 controls the formation of ATM-containing signalling complexes at sites of DNA damage that trigger apoptosis.

    • Young Min Chung
    • , See-Hyoung Park
    •  & Mickey C.-T. Hu
  • Article |

    Changes in gene expression in the hippocampus and the cortex are pivotal for memory consolidation. Gräff and colleagues use a recognition task in mice to show that epigenetic post-translational modifications are rapidly activated in the hippocampus after learning, but induced with a delay in the cortex.

    • Johannes Gräff
    • , Bisrat T. Woldemichael
    •  & Isabelle M. Mansuy
  • Article |

    It is unclear where in the nucleus splicing takes place and how much occurs post-transcriptionally. Using antibodies raised against a phosphorylated splicing factor, Girardet al. show that the majority of splicing occurs co-transcriptionally and that post-transcriptional splicing occurs in nuclear speckles.

    • Cyrille Girard
    • , Cindy L. Will
    •  & Reinhard Lührmann
  • Article
    | Open Access

    The clustered regularly interspaced short palindromic repeats (CRISPR) system protects prokaryotes from foreign DNA. Here, bacteriophage DNA containing mutations that can circumvent this response are shown to be incorporated into the CRISPR locus, allowing bacteria to remember previous infections in an adaptive manner.

    • Kirill A. Datsenko
    • , Ksenia Pougach
    •  & Ekaterina Semenova
  • Article
    | Open Access

    To describe the biochemical composition of an organism multiple data sets must be combined and this information can then be used forin silico analysis. By combining metabolism and transcription data, Lerman et al. discovered new regulons and improved the gene annotation for the simple organism Thermotoga maritima.

    • Joshua A. Lerman
    • , Daniel R. Hyduke
    •  & Bernhard O. Palsson
  • Article |

    Embryonic stem cells have a shortened cell cycle that allows for rapid proliferation, but the exact mechanisms are unclear. Here, a microRNA target, Trim71, is shown to inhibit the expression of a cyclin-dependent kinase inhibitor, thus enabling the G1–S phase cell cycle transition in embryonic stem cells.

    • Hao-Ming Chang
    • , Natalia J. Martinez
    •  & Richard I. Gregory
  • Article
    | Open Access

    Protein L-isoaspartyl methyltransferase (PIMT) is a carboxyl methyltransferase, but its role in regulating the tumour suppressor p53 is unclear. Here, PIMT is shown to methylate p53, obstructing the tumour suppressor function of p53 through reduced protein levels and stability.

    • Jae-Cheol Lee
    • , Sung-Ung Kang
    •  & Jeung-Whan Han
  • Article |

    Chromatin in embryonic stem cells is present in an open state presumably to facilitate gene expression changes required for pluripotency and subsequent multilineage differentiation. This study describes roles for lamin A, histone acetylation and G9a-mediated histone H3 lysine 9 methylation in regulating chromatin plasticity in these cells.

    • Shai Melcer
    • , Hadas Hezroni
    •  & Eran Meshorer
  • Article
    | Open Access

    Synaptic GTPase-activating protein, SynGAP, is a postsynaptic signalling protein that can regulate synaptic function. McMahonet al. express different SynGAP isoforms in neurons and find that the effect on synaptic strength depends on alternative promoter usage and alternative splicing of the C-terminus.

    • A.C. McMahon
    • , M.W. Barnett
    •  & P.C. Kind
  • Article |

    Proteins can undergo folding while being translated by the ribosome, and the extent of this folding is influenced by the rate at which amino acids are added to the nascent chain. This study provides a framework for predicting domain folding probabilities as a function of the kinetics of amino-acid addition.

    • Edward P. O'Brien
    • , Michele Vendruscolo
    •  & Christopher M. Dobson
  • Article |

    SINEs are retrotransposons that insert exact copies of themselves into genomes. Using a marked copy of a SINE, Yadavet al. show that the sequences of newly transposed SINEs are a combination of marked and existing SINEs, suggesting a mechanism for the formation of mosaic SINEs.

    • Vijay Pal Yadav
    • , Prabhat Kumar Mandal
    •  & Sudha Bhattacharya
  • Article |

    Epigenetic and genetic factors have a role in obesity but the role of epigenetics in this disease is unclear. Here, Liet al. investigated global DNA methylation patterns in three breeds of pigs that have different fat contents, providing a resource for the further analysis of differentially methylated gene promoters in obesity.

    • Mingzhou Li
    • , Honglong Wu
    •  & Ruiqiang Li
  • Article
    | Open Access

    Phosphorylation of the carboxy-terminal domain of RNA polymerase II is important for controlling gene transcription. In this study, the transcription elongation factor Tefb is shown to phosphorylate serine-5 and its activity is enhanced when the polymerase is already phosphorylated on serine-7.

    • Nadine Czudnochowski
    • , Christian A. Bösken
    •  & Matthias Geyer
  • Article |

    The bone morphogenetic protein (BMP) and Smad1 signalling pathway is required for embryogenesis. In this study, Smad1 is shown to be phosphorylated by Atm in response to DNA damage and this results in elevated Smad1 signalling, thus uncovering a new role for this pathway in the DNA damage response.

    • Jenny Fung Ling Chau
    • , Deyong Jia
    •  & Baojie Li
  • Article |

    Hox gene expression is induced upon cellular differentiation and is inhibited in pluripotent cells. Bocker and colleagues show that the maintenance of induced transcription depends on Tet2 mediated hydroxylation of 5-methylcytosine at theHoxagene locus, indicating that this epigenetic switch is required for an active chromatin state and gene expression.

    • Michael T. Bocker
    • , Francesca Tuorto
    •  & Achim Breiling
  • Article |

    Adars are adenosine deaminases that act on RNAs, including those encoding proteins involved in neuronal transmission and also Adar RNA. Here, Savvaet al. engineered knock-in Drosophila mutants with altered Adar autoediting and found that this changed the spectrum of adenosine deamination and Drosophilabehaviour.

    • Yiannis A. Savva
    • , James E.C Jepson
    •  & Robert A. Reenan
  • Article |

    Fanconi's anaemia is characterized by an inability to repair DNA damage and is associated with mutations in the Fanconi anaemia nuclear complex, which includes the protein FANCM. This study reports the crystal structures of a fragment of FANCM bound to the histone-fold-containing protein complex, MHF1–MHF2.

    • Yuyong Tao
    • , Changjiang Jin
    •  & Maikun Teng
  • Article |

    Abnormal mitochondrial fission leads to apoptosis and disease. Li and colleagues reveal the mechanism with which the transcription factor Foxo3a suppresses Fis1-mediated mitochondrial fission and apoptosis in cardiomyocytes and adrenocortical cancer cells, which involves miR-484 inhibition of Fis1 translation.

    • Kun Wang
    • , Bo Long
    •  & Pei-Feng Li
  • Article
    | Open Access

    Lysine-specific demethylase 1 (LSD1) removes methyl groups from mono-methylated and dimethylated lysine 4 of histone H3 and represses transcription. In this study, a role for LSD1 in the regulation of genes involved in energy expenditure in adipocytes is reportedin vitroand in mice fed on a high-fat diet.

    • Shinjiro Hino
    • , Akihisa Sakamoto
    •  & Mitsuyoshi Nakao
  • Article
    | Open Access

    Tyrosyl DNA phosphodiesterase 1 (TDP1) repairs DNA breaks and is mutated in the disease Spinocerebellar Ataxia with Axonal Neuropathy. Here TDP1 is shown to be post-translationally modified by sumoylation of lysine 111, and cells carrying a mutation at this residue are inefficient at single-strand DNA break repair.

    • Jessica J.R. Hudson
    • , Shih-Chieh Chiang
    •  & Sherif F. El-Khamisy
  • Article |

    Whether plants can remember their transcriptional response to stress is unknown. By repeatedly exposingArabidopsisto drought, we show that the plants remember their transcriptional response to stress and that the altered genes retain the epigenetic mark H3K4me3 and stalled phosphorylated polymerase II.

    • Yong Ding
    • , Michael Fromm
    •  & Zoya Avramova
  • 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