Testicular germ cell–specific lncRNA, Teshl , is required for complete expression of Y chromosome genes and a normal offspring sex ratio - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Science Advances Année : 2021

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

Résumé

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.
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Dates et versions

inserm-03860768 , version 1 (18-11-2022)

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Citer

Seong Hyeon Hong, Gwidong Han, Seung Jae Lee, Julie Cocquet, Chunghee Cho. Testicular germ cell–specific lncRNA, Teshl , is required for complete expression of Y chromosome genes and a normal offspring sex ratio. Science Advances , 2021, 7 (24), ⟨10.1126/sciadv.abg5177⟩. ⟨inserm-03860768⟩
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