TENT5-mediated polyadenylation of mRNAs encoding secreted proteins is essential for gametogenesis in mice

• Published in: Nature communications Vol. 15; no. 1; pp. 5331 - 20
• Main Authors: Brouze, Michał, Czarnocka-Cieciura, Agnieszka, Gewartowska, Olga, Kusio-Kobiałka, Monika, Jachacy, Kamil, Szpila, Marcin, Tarkowski, Bartosz, Gruchota, Jakub, Krawczyk, Paweł, Mroczek, Seweryn, Borsuk, Ewa, Dziembowski, Andrzej
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/31; 13/51; 14/19; 14/63; 38/47; 38/77; 38/90; 38/91; 45/41; 631/136/2434/1706; 631/136/2434/1822; 631/337/1645/2570; 64/60; Animal models; Animals; Chromosome aberrations; Degeneration; Endoplasmic reticulum; Enzymes; Female; Fertility; Fertility - genetics; Gametocytes; Gametogenesis; Gametogenesis - genetics; Gene sequencing; Humanities and Social Sciences; Infertility; Male; Mammals; Mice; Mice, Inbred C57BL; Mice, Knockout; mRNA; multidisciplinary; Oocytes; Oocytes - metabolism; Oogenesis; Oogenesis - genetics; Polyadenylation; Polynucleotide Adenylyltransferase - genetics; Polynucleotide Adenylyltransferase - metabolism; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Spermatogenesis; Spermatogenesis - genetics; Sterility; Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-49479-4

Cytoplasmic polyadenylation plays a vital role in gametogenesis; however, the participating enzymes and substrates in mammals remain unclear. Using knockout and knock-in mouse models, we describe the essential role of four TENT5 poly(A) polymerases in mouse fertility and gametogenesis. TENT5B and TENT5C play crucial yet redundant roles in oogenesis, with the double knockout of both genes leading to oocyte degeneration. Additionally, TENT5B-GFP knock-in females display a gain-of-function infertility effect, with multiple chromosomal aberrations in ovulated oocytes. TENT5C and TENT5D both regulate different stages of spermatogenesis, as shown by the sterility in males following the knockout of either gene. Finally, Tent5a knockout substantially lowers fertility, although the underlying mechanism is not directly related to gametogenesis. Through direct RNA sequencing, we discovered that TENT5s polyadenylate mRNAs encoding endoplasmic reticulum-targeted proteins essential for gametogenesis. Sequence motif analysis and reporter mRNA assays reveal that the presence of an endoplasmic reticulum-leader sequence represents the primary determinant of TENT5-mediated regulation. Cytoplasmic polyadenylation is vital for gametogenesis, yet key enzymes involved in mammals remain unclear. Here, authors describe how TENT5-mediated polyadenylation of mRNAs encoding secreted proteins is essential for gametogenesis in mice.