Jun Cho1,2,*, Nam-Kyung Yu2,*, Jun-Hyeok Choi2, Su-Eon Sim2, SukJae Joshua Kang2, Chuljung Kwak2, Seung-Woo Lee2, Ji-il Kim2, Dong Il Choi2, V. Narry Kim1,2,†, Bong-Kiun Kaang2,†
1Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea.
2Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
†Corresponding author : V. Narry Kim, Bong-Kiun Kaang
*These authors contributed equally to this work.
Memory stabilization after learning requires translational and transcriptional regulations in the brain, yet the temporal molecular changes that occur after learning have not been explored at the genomic scale. We used ribosome profiling and RNA sequencing to quantify the translational status and transcript levels in the mouse hippocampus after contextual fear conditioning. We revealed three types of repressive regulations: translational suppression of ribosomal protein-coding genes in the hippocampus, learning-induced early translational repression of specific genes, and late persistent suppression of a subset of genes via inhibition of estrogen receptor 1 (ESR1/ERα) signaling. In behavioral analyses, overexpressing Nrsn1, one of the newly identified genes undergoing rapid translational repression, or activating ESR1 in the hippocampus impaired memory formation. Collectively, this study unveils the yet-unappreciated importance of gene repression mechanisms for memory formation.