The nuclear export receptor XPO-1 supports primary miRNA processing in C. elegans and Drosophila.
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.
Büssing
Ingo
I
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Yang
Jr-Shiuan
JS
Lai
Eric C
EC
Grosshans
Helge
H
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D039502:Nuclear Cap-Binding Protein Complex / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D039381:RNA Cap-Binding Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
D028884:Karyopherins; D035683:MicroRNAs; D039502:Nuclear Cap-Binding Protein Complex; D039381:RNA Cap-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein