ILF3 prion-like domain regulates gene expression and fear memory under chronic stress

ストレスの多い状況下でも不快な経験を記憶する能力は、ストレスフルな環境で生きる動物にとって危険回避などの生存戦略に重要だと考えられます。この論文では、マウスの不快記憶形成をストレス状況下でも可能にするためには、NFAR2タンパク質の天然変性領域であるプリオン様ドメインが重要であることを明らかにしました。

Summary: 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 Ilf3 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.

Authors: Yamashita A, Shichino Y, Fujii K, Koshidaka Y, Adachi M, Sasagawa E, Mito M, Nakagawa S, Iwasaki S, Takao K, and Shiina N

Journal: iScience 26, 106229 (2023)

プレスリリース：https://www.nibb.ac.jp/pressroom/news/2023/03/30.html