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Mettl14 and Mettl3 Work Cooperatively to Regulate Retinal Development.

Dan Chen1, Yanling Xin1, Jingyi Guo1

  • 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.

Cell Biochemistry and Function
|December 31, 2024
PubMed
Summary

The study reveals that METTL14 and METTL3 are essential for proper retinal development. Their combined absence disrupts retinal structure and cell distribution, highlighting their cooperative role in the eye.

Keywords:
Mettl14Mettl3N6‐methylenadenosineretinal development

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • N⁶-methyladenosine (m⁶A) is the most prevalent epitranscriptomic modification in eukaryotic messenger RNAs (mRNAs).
  • m⁶A modification regulates diverse aspects of mRNA metabolism and function.
  • The m⁶A methyltransferase complex, including METTL14 and METTL3, plays a key role in its deposition.

Purpose of the Study:

  • To investigate the roles of METTL14 and METTL3 in retinal development using a conditional knockout system.
  • To determine the specific functions of these core m⁶A methyltransferase components in the developing retina.

Main Methods:

  • Utilized the Cre-Loxp conditional knockout system in mice.
  • Generated double knockout models for Mettl14 and Mettl3 in retinal cells.
  • Analyzed retinal structure, cell proliferation, cell generation, and cell distribution.

Main Results:

  • The absence of both Mettl14 and Mettl3 led to significant retinal structural disturbances.
  • Prolonged proliferation of retinal progenitor cells was observed in the double knockout.
  • While cell generation was not affected, the distribution of various retinal cell types was severely disrupted.
  • The combined deletion of Mettl14 and Mettl3 exhibited a more pronounced phenotype compared to the single deletion of Mettl14.

Conclusions:

  • METTL14 and METTL3 function cooperatively in regulating retinal development.
  • These core m⁶A methyltransferases are critical for maintaining retinal structure and proper cell organization.