Mettl14-mediated mA modification ensures the cell-cycle progression of late-born retinal progenitor cells.

Neural progenitor cells lengthen their cell cycle to prime themselves for differentiation as development proceeds. It is currently not clear how they counter this lengthening and avoid being halted in the cell cycle. We show that N-methyladenosine (mA) methylation of cell-cycle-related mRNAs ensures the proper cell-cycle progression of late-born retinal progenitor cells (RPCs), which are born toward the end of retinogenesis and have long cell-cycle length. Conditional deletion of Mettl14, which is required for depositing mA, led to delayed cell-cycle exit of late-born RPCs but has no effect on retinal development prior to birth. mA sequencing and single-cell transcriptomics revealed that mRNAs involved in elongating the cell cycle were highly enriched for mA, which could target them for degradation and guarantee proper cell-cycle progression. In addition, we identified Zfp292 as a target of mA and potent inhibitor of RPC cell-cycle progression.