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

doi:10.1016/j.isci.2023.106229

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

iScience. 2023 Feb 19;26(3):106229. doi: 10.1016/j.isci.2023.106229. eCollection 2023 Mar 17.

Authors

Akira Yamashita^{1

2}, Yuichi Shichino³, Kazuki Fujii^{4

5

6}, Yumie Koshidaka⁵, Mayumi Adachi⁵, Eri Sasagawa⁷, Mari Mito³, Shinichi Nakagawa⁸, Shintaro Iwasaki^{3

9}, Keizo Takao^{4

5

6

7}, Nobuyuki Shiina^{1

2

10}

Affiliations

¹ Laboratory of Neuronal Cell Biology, National Institute for Basic Biology, Okazaki, Aichi 444-8585, Japan.
² Department of Basic Biology, The Graduate University for Advanced Studies, SOKENDAI, Okazaki, Aichi 444-8585, Japan.
³ RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan.
⁴ Department of Behavioral Physiology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan.
⁵ Life Science Research Center, University of Toyama, Toyama 930-0194, Japan.
⁶ Research Center for Idling Brain Science, University of Toyama, Toyama 930-0194, Japan.
⁷ Department of Behavioral Physiology, Graduate School of Innovative Life Science, University of Toyama, Toyama 930-0194, Japan.
⁸ RNA Biology Laboratory, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo Hokkaido 060-0812, Japan.
⁹ Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
¹⁰ Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan.

Abstract

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.

Keywords: Biological sciences; Genetics; Molecular genetics.