Mettl4 limits the proliferation and differentiation of neural stem cells via regulating RNA alternative splicing

Previous studies indicate that Mettl4 regulates gene expression and RNA splicing. However, the biological functions of METTL4 remain unclear. Here we show that the absence of Mettl4 leads to sub lethality in mouse and promotes brain function in processing learning and working memory. The neural stem cells in subgranular zone are more proliferative in Mettl4 knockout mice compared with wild type mice. The proliferation and neurogenesis of primary neural stem cells are increased in the absence of Mettl4. Meanwhile, Mettl4 knockout NSCs are more sensitive low levels of H2O2, which is known to promote proliferation and neurogenesis of neural stem cells. The biological effects caused could be due to the altered gene expression or alternative splicing in neural stem cells when Mettl4 is absent. To investigate the effects at transcriptome level, we performed RNA sequencing. Overall design: Comparative RNA expression and alternative splicing in wild type and Mettl4 knockout neural stem cells extracted from brains at E14.5. The primary NSCs were cultured in vitro.