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Molecular Biology

  • <em>let-7</em> coordinates the transition to adulthood through a single primary and four secondary targets
    Open Access
    let-7 coordinates the transition to adulthood through a single primary and four secondary targets

    Florian Aeschimann, Anca Neagu, Magdalene Rausch, Helge Großhans

    Florian Aeschimann ... Helge Großhans

    Published 25 March 2019

    Although miRNAs may act through regulation of numerous targets, this study shows that the Caenorhabditis elegans let-7 miRNA promotes the juvenile-to-adult transition through repression of LIN41 alone, thereby activating four LIN41 targets that function in pairs to execute distinct developmental functions.

  • Expanding the repertoire of glucocorticoid receptor target genes by engineering genomic response elements
    Open Access
    Expanding the repertoire of glucocorticoid receptor target genes by engineering genomic response elements

    Verena Thormann, Laura V Glaser, Maika C Rothkegel, Marina Borschiwer, Melissa Bothe, Alisa Fuchs, Sebastiaan H Meijsing

    Verena Thormann ... Sebastiaan H Meijsing

    Published 13 March 2019

    This study shows that addition of a single transcription factor binding site can be sufficient to convert a gene into a glucocorticoid receptor target.

  • The small and large ribosomal subunits depend on each other for stability and accumulation
    Open Access
    The small and large ribosomal subunits depend on each other for stability and accumulation

    Brian Gregory, Nusrat Rahman, Ananth Bommakanti, Md Shamsuzzaman, Mamata Thapa, Alana Lescure, Janice M Zengel, Lasse Lindahl

    Brian Gregory ... Lasse Lindahl

    Published 5 March 2019

    Stopping 60S assembly blocks accumulation of 40S by post-assembly turnover, whereas inhibiting 40S assembly allows 60S assembly but results in fragmentation of 25S rRNA.

  • 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.

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