FMRP Modulates Neural Differentiation through m⁶A-Dependent mRNA Nuclear Export.

ABSTRACT: 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 of methylated mRNA targets during neural differentiation. Fmr1 knockout (KO) mice show delayed neural progenitor cell cycle progression and extended maintenance of proliferating neural progenitors into postnatal stages, phenocopying methyltransferase Mettl14 conditional KO (cKO) mice that have no m⁶A modification. RNA-seq and m⁶A-seq reveal that both Mettl14cKO and Fmr1KO lead to the nuclear retention of m⁶A-modified FMRP target mRNAs regulating neural differentiation, indicating that both m⁶A and FMRP are required

SUBMITTER: Edens BM 

PROVIDER: S-EPMC6687293 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature