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Molecular Biology

  • FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress
    Open Access
    FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stress

    Maria Isabel Martinez-Macias, Duncan AQ Moore, Ryan L Green, Fernando Gomez-Herreros, Marcel Naumann, Andreas Hermann, Philip Van Damme, Majid Hafezparast, Keith W Caldecott

    Maria Isabel Martinez-Macias ... Keith W Caldecott

    Published 26 February 2019

    This work shows that the ALS-associated protein FUS is a component of the cellular response to transcriptional stress induced by topoisomerase I–induced DNA breakage, thereby accumulating at sites of nucleolar rRNA synthesis.

  • Main constraints for RNAi induced by expressed long dsRNA in mouse cells
    Open Access
    Main constraints for RNAi induced by expressed long dsRNA in mouse cells

    Tomas Demeter, Michaela Vaskovicova, Radek Malik, Filip Horvat, Josef Pasulka, Eliska Svobodova, Matyas Flemr, Petr Svoboda

    Tomas Demeter ... Petr Svoboda

    Published 26 February 2019

    A systematic survey of dsRNA expression in mouse fibroblasts and embryonic stem cells shows main constraints for RNAi. RNAi activity depends on the initial Dicer cleavage of dsRNA, having implications for the evolution of mammalian RNAi functions.

  • MiR-146a wild-type 3′ sequence identity is dispensable for proper innate immune function in vivo
    Open Access
    MiR-146a wild-type 3′ sequence identity is dispensable for proper innate immune function in vivo

    Grant Bertolet, Natee Kongchan, Rebekah Miller, Ravi K Patel, Antrix Jain, Jong Min Choi, Alexander B Saltzman, Amber Christenson, Sung Yun Jung, Anna Malovannaya, Andrew Grimson, Joel R Neilson

    Grant Bertolet ... Joel R Neilson

    Published 18 February 2019

    Mice engineered to express an allele of a mammalian microRNA in which the 3′ paring specificity of the mature miRNA is robustly altered are phenotypically indistinguishable from mice with the wild-type allele.

  • Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy
    Open Access
    Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy

    Christopher R Heier, Qing Yu, Alyson A Fiorillo, Christopher B Tully, Asya Tucker, Davi A Mazala, Kitipong Uaesoontrachoon, Sadish Srinivassane, Jesse M Damsker, Eric P Hoffman, Kanneboyina Nagaraju, Christopher F Spurney

    Christopher R Heier ... Christopher F Spurney

    Published 11 February 2019

    Vamorolone is a first-in-class dissociative drug that selectively targets the glucocorticoid receptor to safely treat chronic inflammation and the mineralocorticoid receptor to treat cardiomyopathy, providing efficacy with improved safety in mouse models of Duchenne muscular dystrophy.

  • Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund–Thomson syndrome
    Open Access
    Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund–Thomson syndrome

    Hideki Yokoyama, Daniel Moreno-Andres, Susanne A Astrinidis, Yuqing Hao, Marion Weberruss, Anna K Schellhaus, Hongqi Lue, Yoshikazu Haramoto, Oliver J Gruss, Wolfram Antonin

    Hideki Yokoyama ... Wolfram Antonin

    Published 4 February 2019

    RECQL4, which is mutated in the Rothmund–Thomson syndrome characterized by premature aging and cancer susceptibility, is a microtubule-associated protein required for mitotic chromosome alignment.

  • Mitochondrial stress response triggered by defects in protein synthesis quality control
    Open Access
    Mitochondrial stress response triggered by defects in protein synthesis quality control

    Uwe Richter, Kah Ying Ng, Fumi Suomi, Paula Marttinen, Taina Turunen, Christopher Jackson, Anu Suomalainen, Helena Vihinen, Eija Jokitalo, Tuula A Nyman, Marita A Isokallio, James B Stewart, Cecilia Mancini, Alfredo Brusco, Sara Seneca, Anne Lombès, Robert W Taylor, Brendan J Battersby

    Uwe Richter ... Brendan J Battersby

    Published 25 January 2019

    Quality control defects of mitochondrial nascent chain synthesis trigger a sequential stress response characterized by OMA1 activation and ribosome decay, determining mitochondrial form and function.

  • Folding–function relationship of the most common cystic fibrosis–causing CFTR conductance mutants
    Open Access
    Folding–function relationship of the most common cystic fibrosis–causing CFTR conductance mutants

    Marcel van Willigen, Annelotte M Vonk, Hui Ying Yeoh, Evelien Kruisselbrink, Bertrand Kleizen, Cornelis K van der Ent, Maarten R Egmond, Hugo R de Jonge, Ineke Braakman, Jeffrey M Beekman, Peter van der Sluijs

    Marcel van Willigen ... Peter van der Sluijs

    Published 18 January 2019

    The tight correlation between folding and function in cystic fibrosis patients with CFTR mutations of the altered-conductance CFTR class provides an attractive paradigm for characterizing mode of action of novel therapeutics.

  • Rab1b and ARF5 are novel RNA-binding proteins involved in FMDV IRES–driven RNA localization
    Open Access
    Rab1b and ARF5 are novel RNA-binding proteins involved in FMDV IRES–driven RNA localization

    Javier Fernandez-Chamorro, Rosario Francisco-Velilla, Jorge Ramajo, Encarnación Martinez-Salas

    Javier Fernandez-Chamorro ... Encarnación Martinez-Salas

    Published 17 January 2019

    Integration of proteomic data with functional and imaging analysis revealed that Rab1b and ARF5, two ER-Golgi members, are RNA-binding proteins that colocalize with picornavirus IRES-RNA reporters in human cells.

  • Direct binding of Cdt2 to PCNA is important for targeting the CRL4<sup>Cdt2</sup> E3 ligase activity to Cdt1
    Open Access
    Direct binding of Cdt2 to PCNA is important for targeting the CRL4Cdt2 E3 ligase activity to Cdt1

    Akiyo Hayashi, Nickolaos Nikiforos Giakoumakis, Tatjana Heidebrecht, Takashi Ishii, Andreas Panagopoulos, Christophe Caillat, Michiyo Takahara, Richard G Hibbert, Naohiro Suenaga, Magda Stadnik-Spiewak, Tatsuro Takahashi, Yasushi Shiomi, Stavros Taraviras, Eleonore von Castelmur, Zoi Lygerou, Anastassis Perrakis, Hideo Nishitani

    Akiyo Hayashi ... Hideo Nishitani

    Published 31 December 2018

    The C-terminal end of Cdt2 contains a PIP box for binding to PCNA to promote CRL4Cdt2 function, creating a new paradigm where the substrate receptor and substrates bind to a common multivalent docking platform for ubiquitination.

  • Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with MEI4
    Open Access
    Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with MEI4

    Rajeev Kumar, Cecilia Oliver, Christine Brun, Ariadna B Juarez-Martinez, Yara Tarabay, Jan Kadlec, Bernard de Massy

    Rajeev Kumar ... Bernard de Massy

    Published 10 December 2018

    Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with IHO1. Its N-terminal region forms a Pleckstrin homology domain, while its C-terminal region is interacting with MEI4.

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