Nucleocytoplasmic Transport of MicroRNAs and Related Small RNAs

Small RNAs with lengths of 20-30 nucleotides, such as microRNAs (miRNAs), play important regulatory roles in various cellular processes. In conventional linear processing pathways, precursors of miRNAs are transported out of the nucleus by the specific nuclear transport receptor, exportin-5. The exported precursors are further processed and eventually incorporated into the RNA-induced silencing complex (RISC), which silences the expression of the target genes by posttranscriptional mechanisms in the cytoplasm. Subsequent identification and characterization of P-element induced wimpy testis (PIWI)-interacting small RNAs (piRNAs) and endogenous small interfering RNAs (endo-siRNAs) revealed that the processing mechanisms of these newly emerging small RNAs differ from those of miRNAs. Moreover, cumulative experimental evidence indicates that the nuclear functions of the small RNAs, such as transcriptional gene silencing, could be widespread in divergent species. These observations appended other interesting features in the biogenesis and nucleocytoplasmic transport mechanisms of these small RNAs. In this review, we discuss the mechanisms and biological significance of the intracellular trafficking of small RNAs in animal cells.