mA writer complex promotes timely differentiation and survival of retinal progenitor cells in zebrafish.

N-Methyladenosine (mA) is the most prevalent internal modification in eukaryotic mRNAs that modulates mRNA metabolism and function. Most mA modifications on mRNAs are catalyzed by a core writer complex consisting of a methyltransferase, Mettl3, and two ancillary components, Mettl14 and Wtap. Recent studies have demonstrated important roles of mA in various physiological and pathological processes, such as stem cell multipotency, cell differentiation, and cancer progression. However, our knowledge about mA in the retina is still lacking. In this study, we used zebrafish as a model vertebrate to study the function of the mA modification during retinal development. We show that the three main components of the mA writer complex, mettl3, mettl14 and wtap, are abundantly expressed in the developing zebrafish eyes, and that knocking down mA writer complex in zebrafish embryos caused microphthalmia formation, delayed retinal progenitor cells differentiation and increased cell death. By examining the retinal developmental processes in mA writer complex-deficient fish, we show that mA modification regulates zebrafish retinal development through ensuring the timely differentiation and survival of the retinal progenitor cells.