Molecular biology

  • Article |

    Bacterial CRISPR–Cas systems provide adaptive immunity against phage by transcribing interfering RNA from phage DNA inserted into the bacterial genome. Using deep-sequencing, the authors detect a bias in the phage genome locations sampled, suggestive of selection.

    • David Paez-Espino
    • , Wesley Morovic
    •  & Jillian F. Banfield
  • Article |

    Agrobacterium radiobacter strain K84 generates an antibiotic targeting pathogenic strains of Agrobacterium tumefaciens, enabling its use as a biocontrol to prevent infection of crops. Here the authors show that this antibiotic inhibits leucyl-tRNA synthetases via an unusual mechanism that depends on binding of tRNALeu.

    • Shaileja Chopra
    • , Andrés Palencia
    •  & John S. Reader
  • Article
    | Open Access

    RNase P is a key enzyme implicated in transfer RNA maturation that removes the 5′-leader sequences from transfer RNA precursors. In this study, a biophysical characterization of a novel protein-only variant of RNase P, known as PRORP (PROteinaceous RNase P), reveals that transfer RNA recognition by PRORP is similar to that by ribonucleoprotein RNase P.

    • Anthony Gobert
    • , Franziska Pinker
    •  & Philippe Giegé
  • Article |

    The antibiotic streptomycin increases errors in protein translation, but it is unclear how streptomycin exerts its effect on the ribosome. Demirci et al. present X-ray crystal structures that reveal conformational changes induced by streptomycin, which may inspire future efforts in antibiotics design.

    • Hasan Demirci
    • , Frank Murphy IV
    •  & Gerwald Jogl
  • Article |

    Splicing factors, such as the protein SRSF3, regulate mRNA metabolism but are hard to study in vivobecause genetic kockouts are usually lethal. Here, Sen and colleagues create mice with a hepatocyte-specific knockout of Srsf3 and demonstrate its role in hepatocyte differentiation and liver function.

    • Supriya Sen
    • , Hassan Jumaa
    •  & Nicholas J. G. Webster
  • Article |

    NFκB/p65 and PPARγ are both transcription factors that perform distinct but overlapping roles in cellular regulation. Hou et al. report that PPARγ acts as an E3 ubiquitin ligase and promotes Lys48-linked ubiquitination and degradation of p65, terminating NFκB-mediated inflammation and tumorigenesis.

    • Yongzhong Hou
    • , France Moreau
    •  & Kris Chadee
  • Article |

    Tumorigenesis has been likened to a form of cellular reversion to the embryonic state. Ma et al.identify a foetal miRNA as an oncogenic activator of the Wnt/β-catenin pathway in colorectal cancer, whose expression is negatively correlated with survival but is positively correlated with response to adjuvant chemotherapy.

    • Yanlei Ma
    • , Peng Zhang
    •  & Huanlong Qin
  • Article
    | Open Access

    Alternative splicing at the Drosophila Down syndrome cell adhesion molecule gene generates 38,016 isoforms, and underlies self-avoidance of growing neurons. Wang et al. identify a structure in the DSCAM mRNA that ensures mutually exclusive splicing and observe expansion of the structure with increasing number of exons during arthropod evolution.

    • Xuebin Wang
    • , Guoli Li
    •  & Yongfeng Jin
  • Article
    | Open Access

    miRNAs simultaneously regulate a range of genes, making them potential master players in evolution. Huet al.identify a human-specific miRNA called miR-941, whose copy number remains polymorphic in modern humans, and show that miR-941 is expressed in the brain and could regulate important signalling pathways.

    • Hai Yang Hu
    • , Liu He
    •  & Philipp Khaitovich
  • Article
    | Open Access

    Although horizontal gene transfer is prevalent in microorganisms, such sharing of genetic information is thought to be rare in land plants. Focusing on the sequenced moss species,Physcomitrella patens, these authors report genes acquired from microorganisms, which might have facilitated early evolution of land plants.

    • Jipei Yue
    • , Xiangyang Hu
    •  & Jinling Huang
  • Article |

    Microsporidia are widespread human parasites, but limited genome annotation has hampered efforts to understand their biology. Peyretailladeet al. use sequence motifs upstream of start codons to annotate or re-annotate microsporidian genomes and find new genes potentially involved in interactions with the host.

    • Eric Peyretaillade
    • , Nicolas Parisot
    •  & Pierre Peyret
  • Article
    | Open Access

    Heart failure is often a consequence of pathological growth of cardiomyocytes or cardiac hypertrophy. Here Ucar and colleagues report that the microRNAs miR-132 and miR-212 promote cardiac hypertrophy and inhibit autophagy in cardiomyocytes by downregulating the transcription factor FoxO3.

    • Ahmet Ucar
    • , Shashi K. Gupta
    •  & Thomas Thum
  • Article
    | Open Access

    Environmental factors can influence one's susceptibility to cancer, but it is not clear whether such an influence extends beyond the directly exposed generations. Here, feeding pregnant rats with a high-fat diet or a hormone derivative, the authors observe increased breast cancer risk in up to three subsequent generations.

    • Sonia de Assis
    • , Anni Warri
    •  & Leena Hilakivi-Clarke
  • Article |

    Methyltransferases modify cellular proteins in addition to DNA and histones. These authors identify a new family of lysine-specific methyltransferases and show that a member of this family, which is associated with tumour metastasis, methylates the ATP-dependent protein chaperone VCP/p97.

    • Stefan Kernstock
    • , Erna Davydova
    •  & Pål Ø. Falnes
  • Article |

    The mitochondrial transcription factor A (TFAM) mediates both mitochondrial transcription and DNA compaction, but how it achieves these two functions is unknown. In this study, TFAM is shown to slide along DNA and cause local melting, suggesting a mechanism for how TFAM modulates both transcription and compaction.

    • Géraldine Farge
    • , Niels Laurens
    •  & Gijs J.L. Wuite
  • Article
    | Open Access

    The kinase PINK1 is mutated in Parkinson's disease and accumulates in defective mitochondria, where it recruits Parkin. Here, PINK1 is shown to be autophosphorylated and this is required for the localization of PINK1 to mitochondria with a reduced membrane potential, and for the recruitment of Parkin.

    • Kei Okatsu
    • , Toshihiko Oka
    •  & Noriyuki Matsuda
  • 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