Tent4a-KO Mouse

TENT4A, also known as PAPD7, is a non-canonical poly(A) polymerase. It plays a crucial role in regulating multiple biological pathways. It is involved in processes like translesion DNA synthesis (TLS), mRNA stability and translation, and RNA tailing, which are essential for maintaining genomic integrity and proper gene expression [1,2].

In DNA-damage tolerance, TENT4A knockdown leads to reduced amounts of RAD18 protein and DNA polymerase η, resulting in decreased TLS. This indicates its importance in this DNA-repair-related pathway. Bioinformatics analysis also shows that genes related to TLS error-prone DNA polymerases and their TENT4A-related regulators are frequently mutated in endometrial cancer genomes, suggesting a dysregulation of TLS in this cancer [1]. Additionally, depletion of TENT4A and its homolog TENT4B leads to a decrease in mRNA half-life and abundance in cells, highlighting their role in shielding mRNA from rapid deadenylation through generating a mixed poly(A) tail [2].

In summary, TENT4A is essential for regulating mRNA stability and translation, as well as DNA-damage tolerance pathways. The study of TENT4A through gene knockdown models has revealed its significance in endometrial cancer-related DNA-repair dysregulation and mRNA regulation, providing insights into potential disease mechanisms and therapeutic targets.

References:

1. Swain, Umakanta, Friedlander, Gilgi, Sehrawat, Urmila, Geacintov, Nicholas E, Livneh, Zvi. 2021. TENT4A Non-Canonical Poly(A) Polymerase Regulates DNA-Damage Tolerance via Multiple Pathways That Are Mutated in Endometrial Cancer. In International journal of molecular sciences, 22, . doi:10.3390/ijms22136957. https://pubmed.ncbi.nlm.nih.gov/34203408/

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/