title: Multiple repressive mechanisms in the hippocampus during memory formation.
abstract: 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.
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea. Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Nam-Kyung
authors.initials: NK
authors.lastname: Yu
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Jun-Hyeok
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Su-Eon
authors.initials: SE
authors.lastname: Sim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: SukJae Joshua
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Chuljung
authors.initials: C
authors.lastname: Kwak
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Ji-il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Choi
authors.affiliation: Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea. Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea. narrykim@snu.ac.kr kaang@snu.ac.kr.
authors.forename: V Narry
authors.initials: VN
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea. narrykim@snu.ac.kr kaang@snu.ac.kr.
authors.forename: Bong-Kiun
authors.initials: BK
authors.lastname: Kaang
mesh_terms: D000818:Animals; D003214:Conditioning, Classical; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005239:Fear; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; D012269:Ribosomal Proteins; C489067:Nrsn1 protein, mouse