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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues

Published on: December 5, 2016

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FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis

Xu Zhao1, Ying Yang1, Bao-Fa Sun2

  • 11] Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Acaemy of Sciences, No. 1-7 Beichen West Road, Chaoyang District, Beijing 100101, China [2] University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China.

Cell Research
|November 22, 2014
PubMed

Insights

Fat Mass and Obesity-associated protein (FTO) regulates fat cell differentiation by controlling mRNA splicing via N6-methyladenosine (m6A) modification. This discovery reveals a novel mechanism for FTO in adipogenesis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Epigenetics

Background:

  • The function of Fat Mass and Obesity-associated protein (FTO) and its substrate N6-methyladenosine (m6A) in mRNA processing and adipogenesis is not well understood.
  • Adipogenesis, the process of fat cell differentiation, is crucial for metabolic health and is tightly regulated by gene expression and RNA processing.

Purpose of the Study:

  • To investigate the role of FTO and m6A in regulating mRNA processing during adipogenesis.
  • To elucidate the molecular mechanisms by which FTO influences fat cell differentiation.

Main Methods:

  • FTO depletion and restoration experiments in differentiating adipocytes.
  • Transcriptome analysis (RNA-seq) and m6A-seq to profile gene expression and m6A modification.
  • Analysis of RNA-binding protein interactions and mRNA splicing events.

Main Results:

  • FTO expression and m6A levels are inversely correlated during adipogenesis.
  • FTO depletion inhibits adipocyte differentiation; catalytically active FTO is required for differentiation.
  • FTO regulates gene expression and mRNA splicing, with m6A enrichment near splice sites.
  • FTO depletion enhances m6A levels, promoting SRSF2 binding and increasing exon inclusion.
  • FTO controls the splicing of RUNX1T1, a key adipogenic factor, via m6A modulation.

Conclusions:

  • FTO-dependent m6A demethylation is a novel regulatory mechanism in RNA processing.
  • FTO plays a critical role in regulating adipogenesis through modulation of mRNA splicing.

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