Poly(A) RNA polymerase D5 (PAPD5)

Poly(A) RNA polymerase D5 (PAPD5) is a noncanonical polyadenylation enzyme involved in the post-transcriptional regulation of RNA. Unlike canonical poly(A) polymerases, PAPD5 is not primarily responsible for the bulk polyadenylation of mRNAs but instead modifies select RNAs including aberrant, viral, or noncoding RNAs for stability, degradation, or functional modulation. PAPD5 can catalyze both adenylation and, potentially, uridylation of RNAs, which influences RNA decay pathways. It plays a dominant role in the stabilization of hepatitis B viral RNAs, making it a validated target for antiviral therapies such as RG7834 and AB-452. Additionally, PAPD5 dysregulation is implicated in neurodegeneration, as in Huntington’s disease, where it is linked to miRNA instability and neuronal apoptosis. PAPD5’s essential roles in RNA metabolism inform both experimental therapeutic strategies and caution for safety concerns.

Other names

Noncanonical poly(A) polymeraseTerminal nucleotidyltransferaseTRAMP4 component

Inhibition of PAPD5 blocks poly(A) tail stabilization of viral RNA, leading to increased degradation and decreased viral protein production (e.g., HBsAg in HBV) Decreased PAPD5 activity may also impair post-transcriptional regulation and RNA surveillance