Terminal nucleotidyltransferase 4B (TENT4B) (TENT4B)

Terminal nucleotidyltransferase 4B (TENT4B), also known as PAPD5, is a non-canonical poly(A) RNA polymerase that plays a pivotal role in regulating RNA stability [1]. It functions by adding short poly(A) tails to various RNA species, including the telomerase RNA component (TERC) and certain mRNAs, protecting them from degradation by the RNA exosome [4]. In the context of chronic Hepatitis B Virus (HBV) infection, TENT4B is a critical host factor hijacked by the virus to stabilize viral RNAs, particularly those encoding the Hepatitis B surface antigen (HBsAg) [2]. Small molecule inhibitors targeting TENT4B, such as RG7834, disrupt this stabilization process, leading to the rapid degradation of viral transcripts and a significant reduction in HBsAg levels [3]. Beyond its role in virology, TENT4B is essential for telomere maintenance, and its dysfunction is linked to genetic disorders like dyskeratosis congenita and pulmonary fibrosis [4]. As a therapeutic target, TENT4B offers a novel mechanism for achieving a functional cure in HBV patients by suppressing viral protein production [2, 3]. Sources: [1] UniProt Consortium. UniProtKB - Q8NDF8 (TENT4B_HUMAN). [2] Mueller, H., et al. (2019). PAPD5/7 are host factors that are required for Hepatitis B virus RNA stabilization. Science. [3] Boyce, R., et al. (2020). The small molecule RG7834 inhibits a cellular poly(A) polymerase to prevent HBV RNA stabilization. Nature Communications. [4] Shukla, S., et al. (2020). TENT4A and TENT4B (PAPD7 and PAPD5) maintain TERC levels and telomere length. Nucleic Acids Research.

Other names

PAPD5Poly(A) RNA polymerase D5TRF4-2GLD4Terminal uridylyltransferase 3TUT3

Inhibition of the nucleotidyltransferase activity of TENT4B (and its paralog TENT4A), which prevents the stabilization of HBV RNA by mixed tailing, leading to its degradation by the cellular RNA exosome complex [2, 3].