m6A writer complex promotes timely differentiation and survival of retinal progenitor cells in zebrafish

Abstract

N 6 -Methyladenosine (m 6 A) is the most prevalent internal modification in eukaryotic mRNAs that modulates mRNA metabolism and function. Most m 6 A 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 m 6 A in various physiological and pathological processes, such as stem cell multipotency, cell differentiation, and cancer progression. However, our knowledge about m 6 A in the retina is still lacking. In this study, we used zebrafish as a model vertebrate to study the function of the m 6 A modification during retinal development. We show that the three main components of the m 6 A writer complex, mettl3, mettl14 and wtap, are abundantly expressed in the developing zebrafish eyes, and that knocking down m 6 A writer complex in zebrafish embryos caused microphthalmia formation, delayed retinal progenitor cells differentiation and increased cell death. By examining the retinal developmental processes in m 6 A writer complex-deficient fish, we show that m 6 A modification regulates zebrafish retinal development through ensuring the timely differentiation and survival of the retinal progenitor cells.