Yamashita Akira, Shichino Yuichi, Fujii Kazuki, Koshidaka Yumie, Adachi Mayumi, Sasagawa Eri, Mito Mari, Nakagawa Shinichi, Iwasaki Shintaro, Takao Keizo, Shiina Nobuyuki
Laboratory of Neuronal Cell Biology, National Institute for Basic Biology, Okazaki, Aichi 444-8585, Japan.
Department of Basic Biology, The Graduate University for Advanced Studies, SOKENDAI, Okazaki, Aichi 444-8585, Japan.
iScience. 2023 Feb 19;26(3):106229. doi: 10.1016/j.isci.2023.106229. eCollection 2023 Mar 17.
The prion-like domain (PrLD) is a class of intrinsically disordered regions. Although its propensity to form condensates has been studied in the context of neurodegenerative diseases, the physiological role of PrLD remains unclear. Here, we investigated the role of PrLD in the RNA-binding protein NFAR2, generated by a splicing variant of the gene. Removal of the PrLD in mice did not impair the function of NFAR2 required for survival, but did affect the responses to chronic water immersion and restraint stress (WIRS). The PrLD was required for WIRS-sensitive nuclear localization of NFAR2 and WIRS-induced changes in mRNA expression and translation in the amygdala, a fear-related brain region. Consistently, the PrLD conferred resistance to WIRS in fear-associated memory formation. Our study provides insights into the PrLD-dependent role of NFAR2 for chronic stress adaptation in the brain.
朊病毒样结构域（PrLD）是一类内在无序区域。尽管其形成凝聚物的倾向已在神经退行性疾病的背景下进行了研究，但PrLD的生理作用仍不清楚。在这里，我们研究了PrLD在由该基因的剪接变体产生的RNA结合蛋白NFAR2中的作用。去除小鼠体内的PrLD不会损害生存所需的NFAR2功能，但会影响对慢性水浸和束缚应激（WIRS）的反应。PrLD是NFAR2对WIRS敏感的核定位以及WIRS诱导的杏仁核（一个与恐惧相关的脑区）中mRNA表达和翻译变化所必需的。一致地，PrLD在恐惧相关记忆形成中赋予对WIRS的抗性。我们的研究为NFAR2在大脑慢性应激适应中的PrLD依赖性作用提供了见解。
