Nuclear export of microRNA precursors.
MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.
Lund
Elsebet
E
Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA.
Güttinger
Stephan
S
Calado
Angelo
A
Dahlberg
James E
JE
Kutay
Ulrike
U
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins; D009865:Oocytes; D034622:RNA Interference; D012322:RNA Precursors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D014981:Xenopus; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D006160:Guanosine Triphosphate; D028884:Karyopherins; D035683:MicroRNAs; D029543:Nucleocytoplasmic Transport Proteins; D012322:RNA Precursors; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D043244:Ribonuclease III; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C446511:XPO5 protein, human; C503618:XPOT protein, human