Molecular Interplay of PARN and Telomerase: Tail Modifiers and Disease Implications.

Poly(A)-specific ribonuclease (PARN) and telomerase are two indispensable tail-modifying enzymes that are required in two critical cellular processes: the control of the rate of RNA stability and maintenance of telomere integrity, respectively. Pathogenic variations in genes that code for PARN and telomerase complex enzymes have been implicated in several rare genetic diseases, including bone marrow failure syndromes, telomere biology-related disorders, and neoplastic ailments. This is further exemplified by defects in p53 signaling, which not only exacerbate the effects of telomere shortening but also negatively regulate PARN activity, thereby promoting cancer development and accelerated aging. This review examines the molecular interactions between PARN and telomerase, as well as their implications in disease development, with a focus on emerging therapeutic strategies that target the pathways regulated by these two enzymes.