Poly(A) RNA polymerase-associated domain-containing protein 5 (PAPD5)

Poly(A) RNA polymerase-associated domain-containing protein 5 (PAPD5) is a noncanonical poly(A) polymerase located in the nucleus. It adds short poly(A) or oligo(U) tails to a broad range of RNA substrates, marking them for degradation and maintaining RNA surveillance. In hepatitis B virus (HBV) infection, PAPD5 (along with PAPD7 and ZCCHC14) helps stabilize HBV RNAs through post-transcriptional tailing mechanisms, making it a key host dependency factor and a promising antiviral target. Pharmaceutical inhibitors such as AB-452 and RG7834 disrupt PAPD5/7 activity, leading to HBV RNA degradation and reduced viral antigen levels. PAPD5’s functions extend to quality control of aberrant ribosomal and histone mRNAs, as well as discrimination of specific RNA structural forms. Its biological role in RNA metabolism suggests potential relevance in cancer and other diseases involving abnormal RNA processing

Other names

Noncanonical poly(A) polymerase PAPD5Terminal nucleotidyltransferase 5Noncanonical poly(A) RNA polymerase-associated domain-containing protein 5Sometimes grouped with “TRAMP4 complex homolog” or “Cid1-like protein family”

Small-molecule inhibitors block PAPD5/7 activities, destabilizing HBV RNA by interfering with poly(A) tail maintenance and causing viral RNA degradation