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

被引:58
作者
Buessing, Ingo [1 ]
Yang, Jr-Shiuan [2 ]
Lai, Eric C. [2 ]
Grosshans, Helge [1 ]
机构
[1] Friedrich Miescher Inst Biomed Res, CH-4002 Basel, Switzerland
[2] Sloan Kettering Inst, Dept Dev Biol, Rockefeller Res Labs, New York, NY USA
基金
瑞士国家科学基金会;
关键词
CBP20/NCBP-2; CBP80/NCBP-1; microRNA biogenesis; nuclear export; XPO1/CRM1/Embargoed; CAP-BINDING COMPLEX; CAENORHABDITIS-ELEGANS; RNA-INTERFERENCE; MICROPROCESSOR COMPLEX; CELL-DIFFERENTIATION; MICRORNA PRECURSORS; PROTEIN; GENES; GW182; CRM1;
D O I
10.1038/emboj.2010.82
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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
引用
收藏
页码:1830 / 1839
页数:10
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