Poly(A) RNA polymerase non-canonical PAPD5 (PAPD5)

Poly(A) RNA polymerase non-canonical PAPD5 (PAPD5) is an **RNA-processing enzyme** that catalyzes the addition of short poly(A) tails, and sometimes guanosine residues, to the 3′ ends of RNA molecules[1][4]. Unlike canonical poly(A) polymerases, PAPD5 acts in **RNA quality control** by tagging misprocessed, aberrant, or noncoding RNAs for further degradation, thus helping to maintain proper RNA homeostasis in eukaryotic cells[1]. PAPD5 is also a critical host factor in the life cycle of hepatitis B virus (HBV): it protects viral RNA by maintaining the integrity of its poly(A) tails, making it a promising antiviral **therapeutic target**[2][3]. Small-molecule inhibitors such as AB-452 and RG7834 inhibit PAPD5, causing degradation of HBV RNAs and significant reductions in viral protein production[2][3]. The enzyme is a member of the noncanonical poly(A) polymerase family and is sometimes referred to as TENT4B or TRF4-2[4]. There are no widely recognized patient selection or efficacy biomarkers for non-viral diseases at this time.

Other names

Terminal nucleotidyltransferase 4BTENT4BTRF4-2Noncanonical poly(A) polymerase PAPD5hTRF4-2

Inhibition of PAPD5 leads to destabilization of viral RNA (especially HBV RNA) by impairing poly(A) tail maintenance, promoting degradation - Inhibitors prevent the stabilization and correct tailing of viral RNAs, decreasing viral protein expression and replication