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Updated: Jul 28, 2025

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
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Mettl14-mediated m

Liang Li1, Yue Sun2, Alexander E Davis1

  • 1Department of Ophthalmology, Mary M. and Sash A. Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, CA 94304, USA.

Cell Reports
|June 3, 2023
PubMed
Summary
This summary is machine-generated.

N6-methyladenosine (m6A) methylation of cell-cycle mRNAs ensures proper progression of retinal progenitor cells (RPCs). Loss of m6A causes cell-cycle delays, highlighting m6A

Keywords:
CP: Developmental biologyCP: NeuroscienceEpitranscriptomic regulationMettl14Zfp292cell cyclem(6)A mRNA methylationretinal developmentretinal progenitor cells (RPCs)

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Area of Science:

  • Developmental Biology
  • Epigenetics
  • Cell Biology

Background:

  • Neural progenitor cells lengthen their cell cycle during development.
  • The mechanisms preventing cell cycle arrest in these cells are not fully understood.

Purpose of the Study:

  • To investigate the role of N6-methyladenosine (m6A) methylation in regulating cell cycle progression of late-born retinal progenitor cells (RPCs).
  • To identify specific targets of m6A methylation involved in cell cycle control.

Main Methods:

  • Conditional deletion of Mettl14 (an m6A methyltransferase).
  • m6A sequencing (MeRIP-seq).
  • Single-cell transcriptomics.

Main Results:

  • Conditional deletion of Mettl14 delayed cell cycle exit in late-born RPCs without affecting earlier retinal development.
  • m6A sequencing revealed enrichment of m6A in cell-cycle-elongating mRNAs, suggesting their degradation.
  • Zfp292 was identified as an m6A target and a potent inhibitor of RPC cell cycle progression.

Conclusions:

  • m6A methylation is crucial for timely cell cycle progression and differentiation of late-born RPCs.
  • m6A regulates cell cycle by targeting cell-cycle-elongating mRNAs for degradation.
  • Zfp292 is a key downstream effector of m6A in RPC cell cycle control.