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The human cap-binding complex is functionally connected to the nuclear RNA exosome

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  • Peter Refsing Andersen
  • Michal Domanski, Denmark
  • Maiken S Kristiansen, Denmark
  • Helena Storvall, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm
  • ,
  • Evgenia Ntini, Denmark
  • Celine Verheggen, Institute de Génétique Moléculaire Montpellier, CNRS, Montpellier
  • ,
  • Aleks Schein
  • ,
  • Jakob Bunkenborg, Institut for Biokemi og Molekylær Biologi, Denmark
  • Ina Poser, Max Planck Institute of Molecular Biology & Genetics, Dresden
  • ,
  • Marie Hallais, Institute de Génétique Moléculaire Montpellier, CNRS, Montpellier
  • ,
  • Rickard Sandberg, Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm
  • ,
  • Anthony Hyman, Max Planck Institute of Molecular Biology & Genetics, Dresden
  • ,
  • John Lacava, Laboratory of Cellular and Structural Biology, Rockefeller University, New York
  • ,
  • Michael P Rout, Laboratory of Cellular and Structural Biology, Rockefeller University, New York
  • ,
  • Jens Sandberg Andersen, Aalborg University, Denmark
  • Edouard Bertrand, Institute de Génétique Moléculaire Montpellier, CNRS, Montpellier
  • ,
  • Torben Heick Jensen
Nuclear processing and quality control of eukaryotic RNA is mediated by the RNA exosome, which is regulated by accessory factors. However, the mechanism of exosome recruitment to its ribonucleoprotein (RNP) targets remains poorly understood. Here we report a physical link between the human exosome and the cap-binding complex (CBC). The CBC associates with the ARS2 protein to form CBC-ARS2 (CBCA) and then further connects, together with the ZC3H18 protein, to the nuclear exosome targeting (NEXT) complex, thus forming CBC-NEXT (CBCN). RNA immunoprecipitation using CBCN factors as well as the analysis of combinatorial depletion of CBCN and exosome components underscore the functional relevance of CBC-exosome bridging at the level of target RNA. Specifically, CBCA suppresses read-through products of several RNA families by promoting their transcriptional termination. We suggest that the RNP 5' cap links transcription termination to exosomal RNA degradation through CBCN.
Original languageEnglish
JournalNature Structural and Molecular Biology
Volume20
Issue12
Pages (from-to)1367-1376
Number of pages10
ISSN1545-9993
DOIs
Publication statusPublished - 24 Nov 2013

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