Testicular germ cell–specific lncRNA, Teshl , is required for complete expression of Y chromosome genes and a normal offspring sex ratio

Autor: Seung Jae Lee, Chunghee Cho, Seong Hyeon Hong, Gwidong Han, Julie Cocquet
Přispěvatelé: Gwangju Institute of Science and Technology (GIST), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), COCQUET, JULIE
Rok vydání: 2021
Předmět:
Zdroj: Science Advances
Science Advances, 2021, 7 (24), ⟨10.1126/sciadv.abg5177⟩
ISSN: 2375-2548
Popis: International audience; Heat shock factor 2 (HSF2) regulates the transcription of the male-specific region of the mouse Y chromosome long arm (MSYq) multicopy genes only in testes, but the molecular mechanism underlying this tissue specificity remains largely unknown. Here, we report that the testicular germ cell-specific long noncoding RNA (lncRNA), NR_038002, displays a characteristic spatiotemporal expression pattern in the nuclei of round and elongating spermatids. NR_038002-knockout male mice produced sperm with abnormal head morphology and exhibited reduced fertility accompanied by a female-biased sex ratio in offspring. Molecular analyses revealed that NR_038002 interacts with HSF2 and thereby activates expression of the MSYq genes. We designate NR_038002 as testicular germ cell-specific HSF2-interacting lncRNA (Teshl). Together, our study is the first to demonstrate that the testis specificity of HSF2 activity is regulated by the lncRNA Teshl and establishes a Teshl-HSF2-MSYq molecular axis for normal Y-bearing sperm qualities and consequent balanced offspring sex ratio.
Databáze: OpenAIRE