Regulatory discrimination of mRNAs by FMRP controls mouse adult neural stem cell differentiation

Significance Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism. FXS results from the loss of functional fragile X mental retardation protein (FMRP), an RNA binding protein involved in translational regulation. However, the impact of FMRP on gene expression has not been evaluated comprehensively. Here, we present simultaneous high-resolution ribosome profiling and RNA-sequencing data from the same wild-type and FMRP-deficient adult neural stem cells. We find remarkable and heretofore unknown forms of regulation by FMRP critical for neural differentiation. Importantly, our data also show that FMRP controls RNA expression in six distinct ways. Thus, we have uncovered a molecular foundation for pathophysiologies associated with FXS.