Mettl14 介导的 mA 修饰确保了晚期出生的视网膜祖细胞的细胞周期进程。
Mettl14-mediated mA modification ensures the cell-cycle progression of late-born retinal progenitor cells.
机构信息
Department of Ophthalmology, Mary M. and Sash A. Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, CA 94304, USA.
Department of Ophthalmology, Mary M. and Sash A. Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, CA 94304, USA; Department of Neurosurgery, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
出版信息
Cell Rep. 2023 Jun 27;42(6):112596. doi: 10.1016/j.celrep.2023.112596. Epub 2023 Jun 1.
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.
神经祖细胞延长细胞周期，为分化做好准备，随着发育的进行。目前尚不清楚它们如何对抗这种延长，以及如何避免在细胞周期中停滞。我们发现，细胞周期相关 mRNA 的 N6-甲基腺苷（m6A）甲基化确保了晚期视网膜祖细胞（RPC）的适当细胞周期进程，晚期 RPC 是在视网膜发生的末期产生的，其细胞周期较长。条件性敲除 Mettl14（m6A 修饰所必需的）导致晚期 RPC 细胞周期退出延迟，但对出生前的视网膜发育没有影响。m6A 测序和单细胞转录组学显示，参与延长细胞周期的 mRNA 高度富集 m6A，这可以靶向它们进行降解，并保证适当的细胞周期进程。此外，我们还鉴定出 Zfp292 是 m6A 的靶标和 RPC 细胞周期进程的有效抑制剂。
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