Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Active Transport, Cell Nucleus*
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Animals
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Carrier Proteins / metabolism
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Cell Nucleus / metabolism*
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Cytoplasm / metabolism
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Exportin 1 Protein
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Guanosine Triphosphate / metabolism
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HeLa Cells
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Humans
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Karyopherins / metabolism*
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MicroRNAs / chemistry
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MicroRNAs / metabolism*
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Nucleocytoplasmic Transport Proteins*
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Oocytes
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RNA Interference
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RNA Precursors / metabolism*
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RNA, Small Interfering / metabolism
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Receptors, Cytoplasmic and Nuclear*
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Recombinant Proteins / metabolism
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Ribonuclease III / metabolism
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Xenopus
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ran GTP-Binding Protein / metabolism
Substances
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Carrier Proteins
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Karyopherins
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MicroRNAs
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Nucleocytoplasmic Transport Proteins
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RNA Precursors
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RNA, Small Interfering
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Receptors, Cytoplasmic and Nuclear
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Recombinant Proteins
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XPO5 protein, human
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XPOT protein, human
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Guanosine Triphosphate
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Ribonuclease III
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ran GTP-Binding Protein