Microprocessor dynamics and interactions at endogenous imprinted C19MC microRNA genes

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  • Clément Bellemer, Laboratoire de Biologie Moléculaire Eucaryote (LBME), Université Paul Sabatier (UPS), Université de Toulouse, Frankrig
  • Marie-Line Bortolin-Cavaillé, Laboratoire de Biologie Moléculaire Eucaryote (LBME), Université Paul Sabatier (UPS), Université de Toulouse, Frankrig
  • Ute Schmidt, Institute of Molecular Genetics of Montpellier, Frankrig
  • Stig Mølgaard Rask Jensen, Danmark
  • Jørgen Kjems
  • Edouard Bertrand, Institute of Molecular Genetics of Montpellier, Frankrig
  • Jérôme Cavaillé, Laboratoire de Biologie Moléculaire Eucaryote (LBME), Université Paul Sabatier (UPS), Université de Toulouse, Frankrig
Nuclear primary microRNA (pri-miRNA) processing catalyzed by the DGCR8-Drosha (Microprocessor) complex is highly regulated. Little is known, however, about how microRNA biogenesis is spatially organized within the mammalian nucleus. Here, we image for the first time, in living cells and at the level of a single microRNA cluster, the intra-nuclear distribution of untagged, endogenously-expressed pri-miRNAs generated at the human imprinted Chromosome 19 MicroRNA Cluster (C19MC), from the environment of transcription sites to single molecules of fully released DGCR8-bound pri-miRNAs dispersed throughout the nucleoplasm. We report that a large fraction of Microprocessor concentrates onto unspliced C19MC pri-miRNA deposited in close proximity to their genes. Our live-cell imaging studies provide direct visual evidence that DGCR8 and Drosha are targeted post-transcriptionally to C19MC pri-miRNAs as a preformed complex but dissociate separately. These dynamics support the view that, upon pri-miRNA loading and most likely concomitantly with Drosha-mediated cleavages, Microprocessor undergoes conformational changes that trigger the release of Drosha while DGCR8 remains stably bound to pri-miRNA.
OriginalsprogEngelsk
TidsskriftJournal of Cell Science
Vol/bind125
Sider (fra-til)2709-2720
Antal sider12
ISSN0021-9533
DOI
StatusUdgivet - 1 jun. 2012

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