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.
Cell division in eukaryotes requires extensive architectural changes of the nuclear envelope (NE) to ensure that segregated DNA is finally enclosed in a single cell nucleus in each daughter cell. Higher eukaryotic cells have evolved 'open' mitosis, the most extreme mechanism to solve the problem of nuclear division, in which the NE is initially completely disassembled and then reassembled in coordination with DNA segregation. Recent progress in the field has now started to uncover mechanistic and molecular details that underlie the changes in NE reorganization during open mitosis. These studies reveal a tight interplay between NE components and the mitotic machinery.
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