부산대학교 도서관

Poly(A)-specific ribonuclease (PARN) is a 3’-5’ exoribonuclease that removes poly(A) tails of mRNAs and ncRNAs in eukaryotes. Mutations in the human PARN gene are associated with developmental delay and/or telomere biology disorders (TBDs). Here we have established a parn loss-of-function zebrafish model that recapitulates TBD symptoms and phenotypes displayed in human patients. Homozygous parn deficient zebrafish exhibited aberrant snoRNA profile, telomerase RNA maturation and shortening of telomere length over generations. In addition, we found that zygotic parn mutant embryos (Zparn) generated by crossing homozygous male and heterozygous females developed a spectrum of growth/developmental defects from embryonic stage to adult stage. The mutant embryos showed developmental defects with lethality during blastula and gastrulation where the maternal mRNAs need to be destabilized with the activation of zygotic transcription; larvae that surpassed the embryonic stage developed severe developmental defects like bent tail and cardiac edema; the fish that survived to adulthood have severe growth defects. Overall, the array of disease phenotypes observed in PARN mutant fish explains the importance of PARN at different stages of life and could provide a link to the mechanism of TBD penetrance in humans.