The precursor miRNA (premiRNA) is exported to the cytoplasm via Exportin
5 in a Ran GTP-dependent manner, where it is cleaved by Dicer, another RNase III endonuclease which associates with trans-activation response (TAR) RNAbinding protein (TRBP) to produce an miRNAmiRNA* duplex comprising the functional fragment (miRNA) and a low-abundance fragment (miRNA*).
The knockdown effect of shRNAs on the expression of target gene was striking and stable ; however, it might saturate the Exportin
5 pathway of endogenous miRNAs, leading to off-target effects with fatal consequences .
The pre-miRNA is subsequently exported to the cytoplasm by the exportin
and then is cleaved by another ribonuclease III enzyme Dicer to form mature miRNA [1-3].
The import-export machinery responsible for such translocation consists of importins and exportins
. In the following section, the role of specific importin or exportin
molecules in the transport of specific transcription factors involved in allergic inflammation will be discussed.
6: a novel nuclear export receptor that is specific for profilin.actin complexes," The EMBO Journal, vol.
Cullen, "Structural requirements for premicroRNA binding and nuclear export by Exportin
5," Nucleic Acids Research, vol.
Pre-miRNAs are recognized by the Exportin
5 protein and exported out of the nucleus through the nuclear pore complex in a RanGTP-dependent process.
The stem loops are exported into the cytoplasm using Exportin
5 and Ran-GTP and further cleaved by Dicer to yield 21-23 nucleotide duplexes.
Thereafter, this precursor miRNA is exported to the cytoplasm by exportin
Santhanam et al., "Decitabine priming enhances the antileukemic effects of exportin
1 (XPO1) selective inhibitor selinexor in acute myeloid leukemia, " Blood, vol.
This precursor miRNA is then transported across the nuclear envelope to the cytoplasm by the nuclear transport protein, termed exportin
5, where it is further modified by a second RNase enzyme, termed Dicer, which acts in conjunction with a double-stranded RNA-binding protein (TRBP/TARBP2P).
These intermediates are transported by the nuclear export factor exportin
5/Ran GTP into the cytosol, where they are processed into 19- to 25-nucleotide miRNA duplexes by the ribonuclease III Dicer, in association with the transactivation-responsive RNA-binding protein.