Poly(A) RNA polymerase-associated domain-containing protein 7 (PAPD7)

Poly(A) RNA polymerase-associated domain-containing protein 7 (PAPD7) is a non-canonical poly(A) RNA polymerase, also known as terminal nucleotidyltransferase 4A (TENT4A), that catalyzes the addition of heterogeneous nucleotides—primarily adenosine and sometimes guanosine or uridine—at the 3’ end of RNA molecules. Unlike canonical poly(A) polymerases, PAPD7 does not exclusively add poly(A) tails; it can create mixed nucleotide tails, contributing to RNA stabilization by protecting mRNAs from deadenylation. It is involved in the regulation of gene expression, the RNA quality control process, and various RNA metabolic processes, including mRNA processing, histone mRNA turnover, chromosome cohesion, and DNA repair. PAPD7 localizes to several subcellular compartments, including the nucleus, cytosol, Golgi apparatus, mitochondria, lysosome, and sometimes extracellular compartments. It functions as part of a TRAMP-like complex and is a host factor that stabilizes hepatitis B virus (HBV) RNA, making it a therapeutic target for antiviral drugs, particularly in chronic hepatitis B infection. Small molecules such as RG7834 and AB-452 have been identified as inhibitors of PAPD7, with these drugs destabilizing viral mRNA and reducing viral antigen levels in infected cells.

Other names

Terminal nucleotidyltransferase 4ATENT4ACidl1-like proteinPAP-associated domain-containing protein 7

Inhibition of PAPD7 reduces stabilization of viral RNAs (notably HBV), promoting their degradation and reducing viral antigen production Antisense oligonucleotides cause knockdown of PAPD7 mRNA, resulting in reduced HBV antigen output