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

EMBO J. 2010 Jun 2;29(11):1830-9. doi: 10.1038/emboj.2010.82. Epub 2010 Apr 30.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Exportin 1 Protein
  • Karyopherins / genetics
  • Karyopherins / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nuclear Cap-Binding Protein Complex / genetics
  • Nuclear Cap-Binding Protein Complex / metabolism
  • Phenotype
  • RNA Cap-Binding Proteins / genetics
  • RNA Cap-Binding Proteins / metabolism
  • RNA Interference
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Karyopherins
  • MicroRNAs
  • Nuclear Cap-Binding Protein Complex
  • RNA Cap-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear