Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs

TLDR

MicroRNAs are transcribed as long precursors that are processed in the nucleus into ~65‑nt hairpin intermediates (pre‑miRNAs) which are exported to the cytoplasm for further maturation into ~22‑nt miRNAs. Exportin‑5 binds pre‑miRNAs in a Ran‑GTP–dependent manner, mediating their nuclear export. The study demonstrates that Exportin‑5 is essential for nuclear export of pre‑miRNAs and short hairpin RNAs, and that this export is required for miRNA biogenesis and function.

Abstract

MicroRNAs (miRNAs) are initially expressed as long transcripts that are processed in the nucleus to yield approximately 65-nucleotide (nt) RNA hairpin intermediates, termed pre-miRNAs, that are exported to the cytoplasm for additional processing to yield mature, approximately 22-nt miRNAs. Here, we demonstrate that human pre-miRNA nuclear export, and miRNA function, are dependent on Exportin-5. Exportin-5 can bind pre-miRNAs specifically in vitro, but only in the presence of the Ran-GTP cofactor. Short hairpin RNAs, artificial pre-miRNA analogs used to express small interfering RNAs, also depend on Exportin-5 for nuclear export. Together, these findings define an additional cellular cofactor required for miRNA biogenesis and function.