TENT5C, also known as FAM46C, is a non-canonical cytoplasmic poly(A) polymerase. It has diverse functions, including regulating the polyadenylation of mRNAs encoding secreted proteins, which is essential for processes like gametogenesis. It is also involved in pathways related to cancer, with a role in suppressing tumor growth, and in the humoral immune response by regulating immunoglobulin mRNAs [3,5,6]. Gene knockout mouse models have been crucial in studying its functions [3,4,5].

In mouse models, TENT5C and other TENT5 family members are essential for fertility and gametogenesis. TENT5C and TENT5D regulate different stages of spermatogenesis, and TENT5C is required for fastening the flagellum to the sperm head. Its absence leads to abnormal sperm formation and infertility. In B cells, Tent5c-/-mice produce fewer antibodies and have an impaired T-cell-independent immune response, despite having more CD138high plasma cells due to accelerated differentiation. This shows its role in the humoral immune response [3,4,5]. In cancer research, TENT5C functions as a tumor suppressor. It physically interacts with Plk4, inhibits its kinase activity, and suppresses Plk4-induced centriole duplication. Loss of TENT5C has been observed in patient-derived colorectal cancer tumor tissue, and it is associated with prognosis and immune infiltration in colon cancer [1,2].

In conclusion, TENT5C plays essential roles in gametogenesis, the humoral immune response, and cancer development. Gene knockout mouse models have been instrumental in revealing these functions, especially in understanding its role in male infertility and its tumor-suppressing function in various cancers such as colorectal cancer.

References:

1. Kazazian, Karineh, Haffani, Yosr, Ng, Deanna, Wu, Hannah Sun-Tsi, Swallow, Carol Jane. 2020. FAM46C/TENT5C functions as a tumor suppressor through inhibition of Plk4 activity. In Communications biology, 3, 448. doi:10.1038/s42003-020-01161-3. https://pubmed.ncbi.nlm.nih.gov/32807875/

2. Han, Wei, Li, Cheng, Wang, Yongheng, Li, Wenhan, Shi, Wen. 2023. Heme Metabolism-Related Gene TENT5C is a Prognostic Marker and Investigating Its Immunological Role in Colon Cancer. In Pharmacogenomics and personalized medicine, 16, 1127-1143. doi:10.2147/PGPM.S433790. https://pubmed.ncbi.nlm.nih.gov/38152411/

3. Brouze, Michał, Czarnocka-Cieciura, Agnieszka, Gewartowska, Olga, Borsuk, Ewa, Dziembowski, Andrzej. 2024. TENT5-mediated polyadenylation of mRNAs encoding secreted proteins is essential for gametogenesis in mice. In Nature communications, 15, 5331. doi:10.1038/s41467-024-49479-4. https://pubmed.ncbi.nlm.nih.gov/38909026/

4. Baptissart, Marine, Gupta, Ankit, Poirot, Alexander C, Papas, Brian N, Morgan, Marcos. 2025. TENT5C extends Odf1 poly(A) tail to sustain sperm morphogenesis and fertility. In bioRxiv : the preprint server for biology, , . doi:10.1101/2025.03.20.644152. https://pubmed.ncbi.nlm.nih.gov/40196629/

5. Bilska, Aleksandra, Kusio-Kobiałka, Monika, Krawczyk, Paweł S, Dziembowski, Andrzej, Mroczek, Seweryn. 2020. Immunoglobulin expression and the humoral immune response is regulated by the non-canonical poly(A) polymerase TENT5C. In Nature communications, 11, 2032. doi:10.1038/s41467-020-15835-3. https://pubmed.ncbi.nlm.nih.gov/32341344/

6. Lai, Giancarlo, De Grossi, Federica, Catusi, Ilaria, Pesce, Elisa, Manfrini, Nicola. 2024. Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance. In Cancers, 16, . doi:10.3390/cancers16091706. https://pubmed.ncbi.nlm.nih.gov/38730656/