Male mice lacking Teshl lncRNA exhibit inactivation of Y chromosomal multicopy genes and female distortion-biased sex ratio change in offspring
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ABSTRACT: Deletion of multicopy genes located in the male-specific region of the mouse Y chromosome long arm (MSYq) is associated with sperm head abnormalities and male infertility. Heat shock factor 2 (HSF2) regulates the transcription of multicopy genes in MSYq. Little is known how HSF2-dependent regulation of the MSYq genes occurs only in testis. Testis harbors the largest number of tissue-specific long noncoding RNAs (lncRNAs). Here, we report that the novel mouse testis-specific lncRNA NR_038002 is conserved in humans and displayed a spatiotemporal expression pattern in the nucleus of elongating spermatids. NR_038002-deficient male mice produced sperm with abnormal head morphology and exhibited reduced fertility accompanied by female-biased sex ratio change in offspring. Molecular analyses revealed that NR_038002 interacts with HSF2, and thereby activates the expression of the MSYq genes, such as Sycp3 like Y-linked (Sly) and spermiogenesis-specific transcript on the Y (Ssty). We designate NR_038002 as Teshl (testis-specific HSF2-interacting lncRNA). Taken together, our study establishes a molecular relationship of Teshl-HSF2-MSYq, and provides evidence for the critical role of the Teshl-HSF2 complex in acquiring the normal quality of Y-bearing sperm, leading to balanced offspring sex ratio
ORGANISM(S): Mus musculus
PROVIDER: GSE162652 | GEO | 2021/01/01
REPOSITORIES: GEO
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