ILF3 prion-like domain regulates gene expression and fear memory under chronic stress
Akira Yamashita,
Yuichi Shichino,
Kazuki Fujii,
Yumie Koshidaka,
Mayumi Adachi,
Eri Sasagawa,
Mari Mito,
Shinichi Nakagawa,
Shintaro Iwasaki,
Keizo Takao,
Nobuyuki Shiina
Affiliations
Akira Yamashita
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
Yuichi Shichino
RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
Kazuki Fujii
Department of Behavioral Physiology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan; Life Science Research Center, University of Toyama, Toyama 930-0194, Japan; Research Center for Idling Brain Science, University of Toyama, Toyama 930-0194, Japan
Yumie Koshidaka
Life Science Research Center, University of Toyama, Toyama 930-0194, Japan
Mayumi Adachi
Life Science Research Center, University of Toyama, Toyama 930-0194, Japan
Eri Sasagawa
Department of Behavioral Physiology, Graduate School of Innovative Life Science, University of Toyama, Toyama 930-0194, Japan
Mari Mito
RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
Shinichi Nakagawa
RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo Hokkaido 060-0812, Japan
Shintaro Iwasaki
RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan
Keizo Takao
Department of Behavioral Physiology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan; Life Science Research Center, University of Toyama, Toyama 930-0194, Japan; Research Center for Idling Brain Science, University of Toyama, Toyama 930-0194, Japan; Department of Behavioral Physiology, Graduate School of Innovative Life Science, University of Toyama, Toyama 930-0194, Japan
Nobuyuki Shiina
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; Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan; Corresponding author
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.
