Journal
EMBO JOURNAL
Volume 29, Issue 11, Pages 1830-1839Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.82
Keywords
CBP20/NCBP-2; CBP80/NCBP-1; microRNA biogenesis; nuclear export; XPO1/CRM1/Embargoed
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Funding
- SNF [31003A_127052]
- FMI, Novartis Research Foundation
- Sidney Kimmel Cancer Foundation
- Alfred Bressler Scholars Fund
- NIH [R01-GM083300]
- Swiss National Science Foundation (SNF) [31003A_127052] Funding Source: Swiss National Science Foundation (SNF)
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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 CBP80/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. The EMBO Journal (2010) 29, 1830-1839. doi:10.1038/emboj.2010.82; Published online 30 April 2010
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