The deregulation of miRNA function is critical in the pathogenesis of cancer and other diseases. miRNAs and other noncoding RNAs (ncRNAs) tightly regulate gene expression, often in the cell nucleus. Heretofore, there has been no understanding that there exists a general shuttling mechanism that brings miRNAs, in addition to therapeutic oligonucleotides and siRNAs, from the cytoplasm into the nucleus. We have identified this shuttling mechanism, which occurs in response to cell stress. Nuclear imported miRNAs are functional, can potentially alter gene expression, and participate in cell stress response mechanisms. This shuttling mechanism can be augmented to target specific RNAs, including miRNA sponges, and long ncRNAs like Malat-1, which have been implicated in promoting tumor metastasis.