Mettl14 and Mettl3 Work Cooperatively to Regulate Retinal Development

Abstract

N6‐methylenadenosine (m6A) modification, the most abundant epitranscriptomic modification in eukaryotic mRNAs, has been shown to play crucial roles in regulating various aspects of mRNA metabolism and functions. In this study, we applied the Cre‐Loxp conditional knockout system to investigate the role of the core components of the m6A methyltransferase complex, METTL14 and METTL3, in retinal development. Our results showed that the double absence of Mettl14 and Mettl3 caused structural disturbance in the retina and prolonged the proliferation activity of retinal progenitor cells. Interestingly, the deletion of Mettl14 and Mettl3 did not affect the generation of various retinal cells, but severely disrupted their distribution. In addition, double deletion of Mettl14 together with Mettl3 caused a stronger phenotype than did single deletion of Mettl14. In conclusion, our study demonstrated that Mettl14 and Mettl3 work cooperatively to regulate retinal development.