m6A Modification Involves in Enriched Environment-Induced Neurogenesis and Cognition Enhancement

Wenzheng Qu; Qian Li; Mengxuan Wang; Xingsen Zhao; Jiangdong Wu; Diwen Liu; Shenghui Hong; Ying Yang; Qiang Shu; Xuekun Li

doi:10.3389/fcell.2022.903179

m⁶A Modification Involves in Enriched Environment-Induced Neurogenesis and Cognition Enhancement

Front Cell Dev Biol. 2022 Jun 2:10:903179. doi: 10.3389/fcell.2022.903179. eCollection 2022.

Authors

Wenzheng Qu^{1

2}, Qian Li^{1

2}, Mengxuan Wang^{1

2}, Xingsen Zhao^{1

2}, Jiangdong Wu^{1

2}, Diwen Liu³, Shenghui Hong³, Ying Yang^{4

5}, Qiang Shu¹, Xuekun Li^{1

2

6}

Affiliations

¹ The Children's Hospital, National Clinical Research Center for Child Health, School of Medicine, Zhejiang University, Hangzhou, China.
² The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China.
³ Laboratory Animal Center, Zhejiang University, Hangzhou, China.
⁴ CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
⁵ University of Chinese Academy of Sciences, Beijing, China.
⁶ Zhejiang University Cancer Center, Zhejiang University, Hangzhou, China.

Abstract

Although previous studies have shown that an enriched environment (EE) promotes neurogenesis and alters DNA and histone modifications, it remains largely unknown whether an EE affects epitranscriptome in the context of neuronal development. Here, we showed that EE exposure enhanced the pool of adult neural stem/progenitor cells (aNSPCs) and promoted neuronal differentiation of aNSPCs. EE exposure also improved cognitive capabilities and altered the expression of genes relating to neuronal development, neurogenesis, and memory. N ⁶-Methyladenosine (m⁶A) immunoprecipitation combined with deep sequencing (MeRIP-seq) data analysis revealed that EE exposure increased the global level of m⁶A and led to differential m⁶A mRNA modification. Differential m⁶A modification-associated genes are involved in neuronal development, neurogenesis, and so on. Notably, EE exposure decreased the protein level of m⁶A eraser Fto, but did not affect the protein level of m⁶A writers METTL3 and METTL14. Taken together, our results suggest that enriched environment exposure induces differential m⁶A mRNA modification and adds a novel layer to the interaction between the environment and epigenetics in the context of postnatal neuronal development.

Keywords: N6-methyladenosine RNA methylation; cognition; enriched environment; fat mass and obesity-associated gene; neural stem/progenitor cell; neurogenesis; neuronal development.