Drosha-processed microRNAs (miRNAs) have been shown to be exported from the nucleus to the cytoplasm by Exportiñ 5, where they are processed a second time to generate mature miRNAs. In this work we show that miRNAs also use CRM1 for nuclearcytoplasmic 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 RNA5, indicating that this pathway is shared by different classes of processed small RNA5. We also find that CRM1 coimmunoprecipitates with Ago-1, Ago-2, Topo2α. EzH2, and Mta. consistent with a role of Argonautes and small RNAs in chromatin remodeling. [ABSTRACT FROM AUTHOR]