Poly(A)-specific ribonuclease (PARN)

Poly(A)-specific ribonuclease (PARN) is a multi-domain 3′–5′ exoribonuclease that catalyzes the removal of poly(A) tails from the 3’ ends of mRNAs, thereby regulating mRNA stability and translation in eukaryotic cells[1][2][5]. PARN is characterized by its processive, poly(A)-specific exonuclease activity, a requirement for divalent cations (e.g., Mg²⁺) for catalysis, and unique abilities to bind the mRNA 5′ cap and poly(A) tail simultaneously, which enhances processivity and regulation[1][2][3][6]. Structurally, PARN contains several RNA-binding domains—an R3H domain, a nuclease domain, and an RNA recognition motif (RRM)—and exists predominantly as a homodimer, with dimerization essential for catalytic activity[1][2]. Beyond deadenylation, PARN is also involved in telomere maintenance, non-coding RNA maturation, ribosome biogenesis, and regulation of the p53 pathway[4][5]. Dysregulation of PARN expression or function has been reported in various cancers and may contribute to other diseases through defects in RNA processing and genome stability[4][5]. Clinically, PARN is regarded as an enzymatic target of biological interest, but no approved drugs or clinical inhibitors are currently known.

Other names

Poly(A)-specific ribonucleasePARNDeadenylating nucleaseDeadenylation nucleasePolyadenylate-specific ribonucleaseDANDKCB6PFBMFT4

Drugs or molecules modulating PARN would typically act by acting as competitive inhibitors of the active site, disrupting its deadenylation activity, or interfering with essential protein-protein/RNA interactions[1][2]. No specific mechanisms for approved drugs described in the literature.