Terminal nucleotidyltransferase 4A (TENT4A) (PAPD7)

Terminal nucleotidyltransferase 4A (TENT4A), also known as PAPD7, is a non-canonical poly(A) polymerase that plays a critical role in RNA metabolism by adding mixed nucleotide tails (adenosine and guanosine) to the 3' ends of various RNA species [1, 7]. This "mixed tailing" protects transcripts from rapid deadenylation and degradation, thereby enhancing their stability and translation [5, 14]. In the context of infectious disease, the Hepatitis B virus (HBV) hijacks TENT4A and its paralog TENT4B (PAPD5) to stabilize its own viral mRNAs, particularly those encoding the surface antigen (HBsAg) [1, 6]. Small-molecule inhibitors targeting these enzymes have emerged as a promising therapeutic strategy for chronic HBV infection, as they promote the degradation of viral RNA and significantly reduce HBsAg levels [4, 8]. Beyond its role in viral replication, TENT4A is involved in cellular processes such as DNA damage tolerance and telomerase RNA maturation, making it a target of interest in oncology and genetic disorders like dyskeratosis congenita [12, 14].

Other names

Poly(A) RNA polymerase-associated domain-containing protein 7TENT4APOLSTRF4-1TUT3LAK-1DNA polymerase sigma

Inhibition of PAPD7 (often in conjunction with PAPD5) prevents the "mixed tailing" of viral mRNA, leading to its destabilization and degradation, thereby reducing viral protein production and replication [1, 6, 10].