Exosome complex exonuclease RRP44
guanyl-nucleotide exchange factor activity
Human dis3p, which binds to either GTP- or GDP-Ran, complements Saccharomyces cerevisiae dis3.
Saccharomyces cerevisiae Dis3p, which interacts with Ran/Gsp1p, complements Schizosaccharomyces pombe dis3-54. Consistent with the functional conservation of Dis3p in S. cerevisiae and S. pombe, the human ORF (accession number: R27667) was found to be highly homologous to yeast Dis3p. Based on its nucleotide sequence, we cloned a full-sized human DIS3 cDNA. The cloned human cDNA partly but significantly restored the temperature-sensitivity of S. cerevisiae dis3. Thus, Dis3p was found to be structurally and functionally conserved from yeast to mammals. Consistent with the report that S. cerevisiae Dis3p is identical to Rrp44p, which comprises the exosome involved in ribosomal RNA processing, S. cerevisiae Dis3p was found to be localized in the nucleolus. Similar to S. cerevisiae Dis3p, human Dis3p enhanced RCC1-stimulated nucleotide release from Ran, in a dose-dependent manner, and bound to GTP- or GDP-Ran.