TENT5-mediated polyadenylation of mRNAs encoding secreted proteins is essential for gametogenesis in mice.
Nat Commun
; 15(1): 5331, 2024 Jun 22.
Article
em En
| MEDLINE
| ID: mdl-38909026
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espermatogênese
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RNA Mensageiro
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Camundongos Knockout
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Poliadenilação
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Gametogênese
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
/
Nature communications
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Polônia