PRRC2B modulates oligodendrocyte progenitor cell development and myelination by stabilizing Sox2 mRNA
Ying Zhang,
Zhihong Song,
Rong Wu,
Xiangxi Kong,
Hongye Zhang,
Shuoshuo Li,
Xuanwei Gong,
Shenghui Gong,
Jinbo Cheng,
Fang Yuan,
Haitao Wu,
Shukun Wang,
Zengqiang Yuan
Affiliations
Ying Zhang
Beijing Institute of Basic Medical Sciences, Beijing 100850, China
Zhihong Song
Beijing Institute of Basic Medical Sciences, Beijing 100850, China
Rong Wu
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Xiangxi Kong
Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221004, China
Hongye Zhang
Beijing Institute of Basic Medical Sciences, Beijing 100850, China
Shuoshuo Li
Beijing Institute of Basic Medical Sciences, Beijing 100850, China; School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China
Xuanwei Gong
Beijing Institute of Basic Medical Sciences, Beijing 100850, China
Shenghui Gong
Beijing Institute of Basic Medical Sciences, Beijing 100850, China
Jinbo Cheng
Center on Translational Neuroscience, College of Life and Environmental Science, Minzu University of China, Beijing 100081, China; Key Laboratory of Neurology (Hebei Medical University), Ministry of Education, Shijiazhuang 050000, China
Fang Yuan
Department of Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing 100071, China
Haitao Wu
Beijing Institute of Basic Medical Sciences, Beijing 100850, China
Shukun Wang
Beijing Institute of Basic Medical Sciences, Beijing 100850, China; Corresponding author
Zengqiang Yuan
Beijing Institute of Basic Medical Sciences, Beijing 100850, China; Corresponding author
Summary: Oligodendrocyte progenitor cells (OPCs) differentiate into myelin-producing cells and modulate neuronal activity. Defects in OPC development are associated with neurological diseases. N6-methyladenosine (m6A) contributes to neural development; however, the mechanism by which m6A regulates OPC development remains unclear. Here, we demonstrate that PRRC2B is an m6A reader that regulates OPC development and myelination. Nestin-Cre-mediated Prrc2b deletion affects neural stem cell self-renewal and glial differentiation. Moreover, the oligodendroglia lineage-specific deletion of Prrc2b reduces the numbers of OPCs and oligodendrocytes, causing hypomyelination and impaired motor coordination. Integrative methylated RNA immunoprecipitation sequencing, RNA sequencing, and RNA immunoprecipitation sequencing analyses identify Sox2 as the target of PRRC2B. Notably, PRRC2B, displaying separate and cooperative functions with PRRC2A, stabilizes mRNA by binding to m6A motifs in the coding sequence and 3′ UTR of Sox2. In summary, we identify the posttranscriptional regulation of PRRC2B in OPC development, extending the understanding of PRRC2 family proteins and providing a therapeutic target for myelin-related disorders.
