Poly(A)-specific ribonuclease (PARN) (PARN)

Poly(A)-specific ribonuclease (PARN) is a critical magnesium-dependent exoribonuclease that initiates the degradation of mRNA by removing the poly(A) tail, a process known as deadenylation. This enzyme is a key regulator of gene expression, as deadenylation is typically the rate-limiting step in mRNA decay. Beyond its role in general mRNA turnover, PARN is essential for the maturation of the telomerase RNA component (TERC) and other non-coding RNAs. Mutations in PARN are a primary cause of telomere biology disorders, including dyskeratosis congenita and idiopathic pulmonary fibrosis, where the loss of PARN function leads to TERC instability and accelerated telomere shortening. In oncology, PARN is often upregulated and contributes to the stability of mRNAs encoding pro-proliferative factors, making it a potential target for anti-cancer therapy. While there are currently no approved drugs specifically targeting PARN, research is focused on small-molecule inhibitors for cancer and strategies to stabilize telomerase components in deficiency-related diseases.

Other names

Poly-specific ribonucleaseDeadenylating nucleaseDANPolyadenylate-specific ribonuclease

Inhibition of deadenylation, leading to altered mRNA stability and telomere maintenance.