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The nuclear export receptor XPO-1 supports primary miRNA processing in C. elegans and Drosophila

    1. [1] Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    2. [2] Department of Developmental Biology, Sloan-Kettering Institute, Rockefeller Research Laboratories, New York, NY, USA
  • Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 29, Nº. 11, 2010, págs. 1830-1839
  • Idioma: inglés
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  • Resumen
    • MicroRNA (miRNA) biogenesis proceeds from a primary transcript (pri-miRNA) through the pre-miRNA into the mature miRNA. Here, we identify a role of the Caenorhabditis elegans nuclear export receptor XPO-1 and the cap-binding proteins CBP-20/NCBP-2 and CBP-80/NCBP-1 in this process. The RNA-mediated interference of any of these genes causes retarded heterochronic phenotypes similar to those observed for animals with mutations in the let-7 miRNA or core miRNA machinery genes. Moreover, pre- and mature miRNAs become depleted, whereas primary miRNA transcripts accumulate. An involvement of XPO-1 in miRNA biogenesis is conserved in Drosophila, in which knockdown of Embargoed/XPO-1 or its chemical inhibition through leptomycin B causes pri-miRNA accumulation. Our findings demonstrate that XPO-1/Emb promotes the pri-miRNA-to-pre-miRNA processing and we propose that this function involves intranuclear transport and/or nuclear export of primary miRNAs.


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