CRM1 mediates nuclear-cytoplasmic shuttling of mature microRNAs.
Drosha-processed microRNAs (miRNAs) have been shown to be exported from the nucleus to the cytoplasm by Exportin 5, where they are processed a second time to generate mature miRNAs. In this work we show that miRNAs also use CRM1 for nuclear-cytoplasmic shuttling. Inhibition of CRM1 by Leptomycin B results in nuclear accumulation of miRNA guide sequences. Nuclear to cytoplasmic transport can be actively competed by synthetic small interfering RNAs, indicating that this pathway is shared by different classes of processed small RNAs. We also find that CRM1 coimmunoprecipitates with Ago-1, Ago-2, Topo2alpha, EzH2, and Mta, consistent with a role of Argonautes and small RNAs in chromatin remodeling.
Castanotto
Daniela
D
Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, 1450 East Duarte Road, Duarte, CA 91010, USA.
Lingeman
Robert
R
Riggs
Arthur D
AD
Rossi
John J
JJ
D001692:Biological Transport; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D028884:Karyopherins / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D000097606:Exportin 1 Protein
D028884:Karyopherins; D035683:MicroRNAs; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein