FMRP Modulates Neural Differentiation through m6A-Dependent mRNA Nuclear Export

• DOI: 10.1016/j.celrep.2019.06.072
• Publication Date: 2019-07-23T10:39:07Z
• Authors: Brittany M. Edens; Caroline Vissers; Jing Su; Saravanan Arumugam; Zhaofa Xu; Han Shi; Nimrod Miller; Francisca Rojas R...; Guo-li Ming; Chuan He; Hongjun Song; Yongchao C. Ma
• Keywords: Nuclear export signal; FMR1; Neural Development

N6-methyladenosine (m6A) modification of mRNA is emerging as a vital mechanism regulating RNA function. Here, we show that fragile X mental retardation protein (FMRP) reads m6A to promote nuclear export methylated targets during neural differentiation. Fmr1 knockout (KO) mice delayed progenitor cell cycle progression and extended maintenance proliferating progenitors into postnatal stages, phenocopying methyltransferase Mettl14 conditional KO (cKO) have no modification. RNA-seq m6A-seq reveal both Mettl14cKO Fmr1KO lead the retention m6A-modified FMRP target mRNAs differentiation, indicating are required for mRNAs. preferentially binds RNAs facilitate their through CRM1. The defect can be mitigated by wild-type but not export-deficient FMRP, establishing critical role in mediating m6A-dependent