Terminal nucleotidyltransferase 4B (PAPD5) (PAPD5)

Terminal nucleotidyltransferase 4B (PAPD5), also known as TENT4B, is a non-canonical poly(A) RNA polymerase that plays a pivotal role in the regulation of RNA stability and quality control. Unlike canonical poly(A) polymerases that stabilize mRNA for translation, PAPD5 typically adds short oligo(A) or mixed tails to various RNA species, often marking them for degradation by the RNA exosome. In the context of chronic Hepatitis B (CHB), the virus hijacks PAPD5 to stabilize its own transcripts; the enzyme incorporates guanosine residues into the viral poly(A) tail, creating a "shield" that prevents host-mediated deadenylation and degradation. Consequently, PAPD5 has emerged as a major therapeutic target for HBV "functional cure" strategies, as its inhibition leads to the rapid degradation of viral RNA and a significant reduction in hepatitis B surface antigen (HBsAg) levels. Beyond virology, PAPD5 is a key target in telomere biology, where it destabilizes the telomerase RNA component (TERC). Inhibiting PAPD5 in patients with telomeropathies, such as dyskeratosis congenita, can restore TERC levels and telomerase activity, offering a potential treatment for bone marrow failure and other aging-related conditions.

Other names

TENT4BPoly(A) RNA polymerase-associated domain-containing protein 5TRF4-2TUTase 3Terminal uridylyltransferase 3Topoisomerase-related function protein 4-2P53 activator protein 5

Inhibition of PAPD5 enzymatic activity to destabilize HBV RNA by preventing guanylation of the poly(A) tail, or to stabilize TERC by preventing its oligoadenylation and subsequent exosomal degradation.