High impact information on XPO5

• Primary microRNA transcripts are processed by the RNaseIII nuclease, Drosha, and are exported from the nucleus by Exportin-5 [1].
• Short hairpin RNAs, artificial pre-miRNA analogs used to express small interfering RNAs, also depend on Exportin-5 for nuclear export [2].
• EBER1 does not bind exportin 5; therefore, it is unlikely to act by interfering with microRNA biogenesis [3].
• Exp5 stimulates nuclear export of eEF1A when microinjected into the nucleus of Xenopus laevis oocytes [4].
• Indeed, not only the canonical tRNA export receptor, exportin-t, but also Exp5 can drive nuclear export of tRNA [4].

Biological context of XPO5

• Exportin-5 is a nuclear export receptor for certain classes of double-stranded RNA (dsRNA), including pre-micro-RNAs, viral hairpin RNAs, and some tRNAs [5].
• Exportin-5 stimulates JAZ shuttling, and gene silencing of exportin-5 reduces shuttling [5].
• Using microinjection in the nucleus of HeLa cells and transfection experiments, we show here that formation of the cooperative RanGTP-dependent RNA/ILF3/exportin-5 complex promotes the co-transport of VA1 and ILF3 from the nucleus to the cytoplasm [6].
• Its accumulation in the nucleus and export to the cytoplasm required the phosphorylation site Ser-194, which was also required for its interaction with the nucleocytoplasmic shuttling protein exportin-5 [7].
• Overexpression of exportin 5 enhances RNA interference mediated by short hairpin RNAs and microRNAs [8].

Anatomical context of XPO5

• The knockdown of Drosophila exportin-5 in cultured cells decreased the amounts of tRNA as well as miRNA, whereas the knock down of human exportin-5 in cultured cells affected only miRNA but not tRNA levels [9].

Associations of XPO5 with chemical compounds

• 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 [10].
• Of the five expansin genes expressed in control roots, two alpha-expansins (Exp1 and Exp5) and two beta-expansins (ExpB2 and ExpB8) are expressed specifically in the growing region, whereas expression of beta-expansin ExpB6 is shifted basipetally [11].

Physical interactions of XPO5

• We found that JAZ binds to exportin-5 in a Ran-GTP- and dsRNA-dependent manner [5].
• Minihelix-containing RNAs mediate exportin-5-dependent nuclear export of the double-stranded RNA-binding protein ILF3 [6].
• We have identified eukaryotic elongation factor 1A (eEF1A) and tRNA as RanGTP-dependent binding partners of exportin-5 (Exp5) [4].

Regulatory relationships of XPO5

• Recombinant exportin-5 also stimulates nuclear export of JAZ in permeabilized cells [5].

Other interactions of XPO5

• Together, these data suggest that JAZ is exported by exportin-5 but translocates back into nuclei by a facilitated diffusion mechanism [5].
• Formation of this complex is facilitated by the ability of both exportin-5 and ILF3 to mutually increase their apparent affinity for VA1 RNA [6].
• These results indicate that double-stranded RNA binding ability is an inherited functional characteristic of the exportin-5 orthologues and that Drosophila exportin-5 functions as an exporter of tRNAs as well as pre-miRNAs in the fruit fly that lacks the orthologous gene for exportin-t [9].
• Exportin-5, an evolutionarily conserved nuclear export factor belonging to the importin-beta family of proteins, is known to play a role in the nuclear export of small noncoding RNAs such as precursors of microRNA, viral minihelix RNA and a subset of tRNAs in mammalian cells [9].
• The discrepancy between pri-miRNA and miR expression following overload was not explained by a change in the expression of components of the miRNA biogenesis pathway, since Drosha and Exportin-5 transcript levels were significantly increased by 50% in response to functional overload, whereas Dicer expression remained unchanged [12].

Analytical, diagnostic and therapeutic context of XPO5

• Gel retardation assays revealed that exportin-5 directly interacts with VA1 RNA in a RanGTP-dependent manner [13].
• An unbiased affinity chromatography approach with immobilized pre-miRNAs identified exportin 5 as the pre-miRNA-specific export carrier [14].

References