Testicular germ cell-specific lncRNA, <i>Teshl</i>, is required for complete expression of Y chromosome genes and a normal offspring sex ratio.

Abstract

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), <i>NR_038002</i>, displays a characteristic spatiotemporal expression pattern in the nuclei of round and elongating spermatids. <i>NR_038002</i>-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 <i>NR_038002</i> interacts with HSF2 and thereby activates expression of the MSYq genes. We designate <i>NR_038002</i> as testicular germ cell-specific HSF2-interacting lncRNA (<i>Teshl</i>). Together, our study is the first to demonstrate that the testis specificity of HSF2 activity is regulated by the lncRNA <i>Teshl</i> and establishes a <i>Teshl</i>-HSF2-MSYq molecular axis for normal Y-bearing sperm qualities and consequent balanced offspring sex ratio.