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The crosstalk between RNA m6A epitranscriptome and TGFβ signaling pathway contributes to the arrest of cell cycle

Le Li1, Yong-Xian Chen1, Bing Yang2

  • 1Center for Bioresources and Drug Discovery and School of Biosciences and Biopharmaceutics, Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.

Gene
|February 20, 2020
PubMed

Insights

TGFβ signaling regulates cell growth. This study reveals that N6-methyl-adenosine (m6A) RNA modification is elevated by TGFβ, impacting cell cycle arrest and growth inhibition.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • TGFβ signaling is crucial for cell processes like division and differentiation, with dysregulation linked to cancer.
  • N6-methyl-adenosine (m6A) is a prevalent mRNA modification, but its response to TGFβ stimulation is not well understood.

Purpose of the Study:

  • To investigate the relationship between TGFβ signaling and the m6A epitranscriptome.
  • To elucidate the role of m6A modifications in TGFβ-mediated cell cycle regulation and growth inhibition.

Main Methods:

  • MCF7 cells were treated with TGFβ, and cellular m6A levels were assessed.
  • MeRIP-sequencing was performed on mRNA from TGFβ-treated and untreated MCF7 cells.
  • WTAP was silenced using knockdown techniques to evaluate its role.

Main Results:

  • TGFβ treatment increased cellular RNA m6A levels, potentially via WTAP and METTL3 upregulation.
  • m6A-modified mRNAs were enriched in the TGFβ signaling pathway.
  • WTAP knockdown impaired TGFβ-induced SMAD2/3 phosphorylation and reversed TGFβ-mediated growth inhibition.
  • TGFβ increased m6A modification and mRNA levels of the cell cycle inhibitor JunB, which was reversed by WTAP knockdown.

Conclusions:

  • The m6A pathway plays a critical role in TGFβ-induced cell cycle arrest.
  • These findings offer new mechanistic insights into TGFβ-mediated growth inhibition and its connection to the epitranscriptome.
Keywords:
Cell cycleEpitranscriptomeN6-methyladenosineTGFβWTAP

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