Tent4b-KO Mouse

Tent4b, also known as Papd5, is a terminal nucleotidyl-transferase that is part of the RNA tailing machinery. It plays crucial roles in post-transcriptional gene regulation, specifically in modifying the 3'-ends of RNA molecules. It adds nucleotides to RNA, influencing functions such as protein synthesis, RNA stability, and mRNA translation and decay [2,4]. This enzyme is involved in pathways like amyloidogenic phase transition, mRNA deadenylation regulation, and host RNA quality control [1,2,3]. Genetic models, like KO/CKO mouse models, can be valuable for studying its in-vivo functions.

In the amyloidogenic phase transition, a targeted RNA interference screen identified Tent4b as an essential participant in the transition of nucleoli into amyloid bodies. It synthesizes starRNA, a class of long untemplated RNAs that act as polyanionic stimulators of amyloidogenesis [1]. In mRNA regulation, Tent4b, along with Tent4a, is responsible for mRNA guanylation, generating a mixed poly(A) tail. A single guanosine residue added by Tent4b can impede the deadenylase CCR4-NOT complex, protecting mRNA from rapid deadenylation. Depletion of Tent4a and Tent4b leads to decreased mRNA half-life and abundance in cells [2]. In host RNA quality control, inhibition of Tent4b (Papd5) with a small molecule results in rapid and selective degradation of hepatitis B virus (HBV) RNA, reducing viral gene products [3].

In conclusion, Tent4b is a key enzyme in RNA tailing, significantly influencing RNA-related biological processes. Its study through model-based research, especially KO/CKO mouse models, could potentially lead to a better understanding of amyloid-related diseases and hepatitis B, offering new insights for disease treatment strategies.

References:

1. Bokros, Michael, Balukoff, Nathan C, Grunfeld, Alex, Bourgault, Steve, Lee, Stephen. 2024. RNA tailing machinery drives amyloidogenic phase transition. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2316734121. doi:10.1073/pnas.2316734121. https://pubmed.ncbi.nlm.nih.gov/38805292/

2. Lim, Jaechul, Kim, Dongwan, Lee, Young-Suk, Ahn, Kwangseog, Kim, V Narry. 2018. Mixed tailing by TENT4A and TENT4B shields mRNA from rapid deadenylation. In Science (New York, N.Y.), 361, 701-704. doi:10.1126/science.aam5794. https://pubmed.ncbi.nlm.nih.gov/30026317/

3. Block, Timothy M, Young, John A T, Javanbakht, Hassan, Sofia, Michael J, Zhou, Tianlun. 2020. Host RNA quality control as a hepatitis B antiviral target. In Antiviral research, 186, 104972. doi:10.1016/j.antiviral.2020.104972. https://pubmed.ncbi.nlm.nih.gov/33242518/

4. Menezes, Miriam R, Balzeau, Julien, Hagan, John P. 2018. 3' RNA Uridylation in Epitranscriptomics, Gene Regulation, and Disease. In Frontiers in molecular biosciences, 5, 61. doi:10.3389/fmolb.2018.00061. https://pubmed.ncbi.nlm.nih.gov/30057901/