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The primary miRNAs are cleaved by ribonuclease III Drosha and the double-stranded DNA binding protein Pasha/DGCR8 into a 70- to 100-nucleotide stem loop structure pre-miRNAs, which are exported to the cytoplasm by exportin 5/Ran GTP.
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*).
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.
Thereafter, this precursor miRNA is exported to the cytoplasm by exportin 5.
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).