Takaoka Shohei, Yanagiya Akiko, Mohamed Haytham Mohamed Aly, Higa Rei, Abe Takaya, Inoue Ken-Ichi, Takahashi Akinori, Stoney Patrick, Yamamoto Tadashi
Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan.
Department of Bioresources Engineering, National Institute of Technology, Okinawa College, 905 Henoko, Nago, Okinawa 905-2192, Japan.
iScience. 2021 Sep 21;24(10):103151. doi: 10.1016/j.isci.2021.103151. eCollection 2021 Oct 22.
Control of mRNA stability and degradation is essential for appropriate gene expression, and its dysregulation causes various disorders, including cancer, neurodegenerative diseases, diabetes, and obesity. The 5'-3' exoribonuclease XRN1 executes the last step of RNA decay, but its physiological impact is not well understood. To address this, forebrain-specific conditional knockout mice (-cKO) were generated, as 1 null mice were embryonic lethal. -cKO mice exhibited obesity with leptin resistance, hyperglycemia, hyperphagia, and decreased energy expenditure. Obesity resulted from dysregulated communication between the central nervous system and peripheral tissues. Moreover, expression of mRNAs encoding proteins that regulate appetite and energy expenditure was dysregulated in the hypothalamus of -cKO mice. Therefore, we propose that XRN1 function in the hypothalamus is critical for maintenance of metabolic homeostasis.
控制信使核糖核酸（mRNA）的稳定性和降解对于适当的基因表达至关重要，其失调会导致各种疾病，包括癌症、神经退行性疾病、糖尿病和肥胖症。5'-3'外切核糖核酸酶XRN1执行RNA降解的最后一步，但其生理影响尚未得到充分了解。为了解决这个问题，由于纯合缺失小鼠胚胎致死，因此构建了前脑特异性条件性敲除小鼠（-cKO）。-cKO小鼠表现出肥胖并伴有瘦素抵抗、高血糖、食欲亢进和能量消耗减少。肥胖是由中枢神经系统和外周组织之间的通讯失调引起的。此外，在-cKO小鼠的下丘脑中，编码调节食欲和能量消耗蛋白质的mRNA表达失调。因此，我们认为XRN1在下丘脑中的功能对于维持代谢稳态至关重要。
