page_title: XPO5
section_title: Binding to pre-miRNA
hierarchical_section_title: XPO5 / Mechanism / Binding to pre-miRNA
caption_attribution_description: English: Image of XPO5 created in PyMol using the crystal structure from entry 3A6P in the Protein Data Bank. XPO5 is labeled green, Ran is labeled red, RNA is multi-colored, and GTP is labeled white.
context_page_description: Exportin-5 is a protein that, in humans, is encoded by the XPO5 gene. In eukaryotic cells, the primary purpose of XPO5 is to export pre-microRNA out of the nucleus and into the cytoplasm, for further processing by the Dicer enzyme. Once in the cytoplasm, the microRNA can act as a gene silencer by regulating translation of mRNA. Although XPO5 is primarily involved in the transport of pre-miRNA, it has also been reported to transport tRNA.
  Much research on XPO5 is ongoing. miRNA is a prominent research topic due to its potential use as a therapeutic, with several miRNA-based drugs already in use.
context_section_description: After RanGTP binds to XPO5, the XPO5-RanGTP complex forms a U-like structure to hold the pre-miRNA. The XPO5-RanGTP complex recognizes pre-miRNA by its two-nucleotide 3’ overhang—a sequence consisting of two bases at the 3’ end of the pre-miRNA that are not paired with other bases. This motif is unique to pre-miRNA, and by recognizing it XPO5 ensures specificity for transporting only pre-miRNA. On its own, pre-miRNA is in a “closed” conformation, with the 3’ overhang flipped up toward the RNA minor groove. However, upon binding to XPO5, the 3’ overhang is flipped downwards away from the rest of the pre-miRNA molecule into an “open” conformation. This helps the backbone phosphates of these two nucleotides form hydrogen bonds with many XPO5 residues, allowing XPO5 to recognize the RNA as pre-miRNA. Because these interactions involve only the RNA phosphate backbone, they are nonspecific and allow XPO5 to recognize and transport any pre-miRNA. The rest of the pre-miRNA stem binds to XPO5 via interactions between the negatively-charged phosphate backbone and several positively-charged interior XPO5 residues.
caption: Image of XPO5 ternary complex generated in PyMol from crystal structure entry 3A6P in the Protein Data Bank. XPO5 is labeled green, Ran is labeled red, RNA is multi-colored, and GTP is labeled white.[14]
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