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  1. Article ; Online: Cyclin B/CDK1 and Cyclin A/CDK2 phosphorylate DENR to promote mitotic protein translation and faithful cell division

    Katharina Clemm von Hohenberg / Sandra Müller / Sibylle Schleich / Matthias Meister / Jonathan Bohlen / Thomas G. Hofmann / Aurelio A. Teleman

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 14

    Abstract: The cell cycle regulates translation during mitosis by controlling DENR stability. Here, the authors show the non-canonical translation initiation complex DENR·MCTS1 is phosphorylated during mitosis by CDK1 and 2, enabling the translation of genes needed ...

    Abstract The cell cycle regulates translation during mitosis by controlling DENR stability. Here, the authors show the non-canonical translation initiation complex DENR·MCTS1 is phosphorylated during mitosis by CDK1 and 2, enabling the translation of genes needed for proper mitotic progression.
    Keywords Science ; Q
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe

    Gaspard Kerner / Anna-Lena Neehus / Quentin Philippot / Jonathan Bohlen / Darawan Rinchai / Nacim Kerrouche / Anne Puel / Shen-Ying Zhang / Stéphanie Boisson-Dupuis / Laurent Abel / Jean-Laurent Casanova / Etienne Patin / Guillaume Laval / Lluis Quintana-Murci

    Cell Genomics, Vol 3, Iss 2, Pp 100248- (2023)

    2023  

    Abstract: Summary: Ancient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day ... ...

    Abstract Summary: Ancient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day inflammatory disease risk. Here, we use an ancestry-aware approximate Bayesian computation framework to estimate the nature, strength, and time of onset of selection acting on 2,879 ancient and modern European genomes from the last 10,000 years. We found that the bulk of genetic adaptation occurred after the start of the Bronze Age, <4,500 years ago, and was enriched in genes relating to host-pathogen interactions. Furthermore, we detected directional selection acting on specific leukocytic lineages and experimentally demonstrated that the strongest negatively selected candidate variant in immunity genes, lipopolysaccharide-binding protein (LBP) D283G, is hypomorphic. Finally, our analyses suggest that the risk of inflammatory disorders has increased in post-Neolithic Europeans, possibly because of antagonistic pleiotropy following genetic adaptation to pathogens.
    Keywords ancient DNA ; immunity ; host defense ; natural selection ; local adaptation ; inflammatory disorders ; Genetics ; QH426-470 ; Internal medicine ; RC31-1245
    Subject code 930
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: DENR promotes translation reinitiation via ribosome recycling to drive expression of oncogenes including ATF4

    Jonathan Bohlen / Liza Harbrecht / Saioa Blanco / Katharina Clemm von Hohenberg / Kai Fenzl / Günter Kramer / Bernd Bukau / Aurelio A. Teleman

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 15

    Abstract: Upon stress, translation of ATF4 is induced by reinitiating ribosomes following translation of short upstream open reading frames (uORFs). Here the authors show that translation re-initiation of ATF4 is mediated by the DENR-MCTS1 complex which acts on ... ...

    Abstract Upon stress, translation of ATF4 is induced by reinitiating ribosomes following translation of short upstream open reading frames (uORFs). Here the authors show that translation re-initiation of ATF4 is mediated by the DENR-MCTS1 complex which acts on uORFs containing certain penultimate codons.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation.

    Yasar Luqman Ahmed / Sibylle Schleich / Jonathan Bohlen / Nicolas Mandel / Bernd Simon / Irmgard Sinning / Aurelio A Teleman

    PLoS Biology, Vol 16, Iss 6, p e

    2018  Volume 2005160

    Abstract: The succession of molecular events leading to eukaryotic translation reinitiation-whereby ribosomes terminate translation of a short open reading frame (ORF), resume scanning, and then translate a second ORF on the same mRNA-is not well understood. ... ...

    Abstract The succession of molecular events leading to eukaryotic translation reinitiation-whereby ribosomes terminate translation of a short open reading frame (ORF), resume scanning, and then translate a second ORF on the same mRNA-is not well understood. Density-regulated reinitiation and release factor (DENR) and multiple copies in T-cell lymphoma-1 (MCTS1) are implicated in promoting translation reinitiation both in vitro in translation extracts and in vivo. We present here the crystal structure of MCTS1 bound to a fragment of DENR. Based on this structure, we identify and experimentally validate that DENR residues Glu42, Tyr43, and Tyr46 are important for MCTS1 binding and that MCTS1 residue Phe104 is important for tRNA binding. Mutation of these residues reveals that DENR-MCTS1 dimerization and tRNA binding are both necessary for DENR and MCTS1 to promote translation reinitiation in human cells. These findings thereby link individual residues of DENR and MCTS1 to specific molecular functions of the complex. Since DENR-MCTS1 can bind tRNA in the absence of the ribosome, this suggests the DENR-MCTS1 complex could recruit tRNA to the ribosome during reinitiation analogously to the eukaryotic initiation factor 2 (eIF2) complex in cap-dependent translation.
    Keywords Biology (General) ; QH301-705.5
    Subject code 410
    Language English
    Publishing date 2018-06-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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