Role of PARN gene in telomere maintenance in a zebrafish model

The telomeres are highly conserved repetitive DNA sequence elements present at the ends of linear chromosome. These structures function as a biological clock of the cell since telomeres become shorter with each replication cycle and finally reach a critical threshold in their length after which the cell enters senescence. The pathogenic mutations in genes encoding various proteins involved in telomere maintenance, lead to critically short or abnormal telomeres. The group of disorders characterised by such short telomeres are termed telomere biology disorders(TBDs). Recent studies have shown that the gene PARN, which encodes poly(A)-specific ribonuclease, a deadenylating enzyme, as one of the genes leading to development of TBDs. There are very limited number of reports on the impact of PARN on TBDs especially in animal models. In this study, we have identified different mutant alleles of parn present in the zebrafish genome. We have determined the telomere lengths of these fish using qPCR assay technique and found that there is a shortening of telomeres in carriers of mutant alleles. There is also strong evidence of progressive shortening of telomeres in fish carrying certain mutant alleles over four generations