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RNA decay in processing bodies is indispensable for adipogenesis.

Ryotaro Maeda1, Daisuke Kami2, Akira Shikuma1

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RNA decay, regulated by Ddx6 and 4E-T in processing bodies (PBs), is crucial for adipogenesis. Loss of these factors prevents adipocyte differentiation by maintaining inhibitory gene expression.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Gene Regulation

Background:

  • Adipogenesis is a complex differentiation process.
  • RNA metabolism's role in adipogenesis is not well understood.
  • Ddx6 is a key protein in RNA decay and translational repression.

Purpose of the Study:

  • To investigate the role of Ddx6 and its binding partner 4E-T in adipogenesis.
  • To elucidate the mechanism by which RNA decay contributes to adipocyte differentiation.

Main Methods:

  • Adipogenic induction of preadipocytes.
  • Ddx6 knockout (KO) and 4E-T knockdown (KD) models.
  • Analysis of processing body (PB) formation.
  • Gene expression analysis of adipogenic regulators.

Main Results:

  • Ddx6 and 4E-T dynamically accumulated to form PBs during early adipogenesis.
  • Ddx6 KO or 4E-T KD suppressed adipogenesis and PB formation.
  • Failure to downregulate key transcription factors and negative adipogenic regulators was observed in KO/KD cells.
  • Eliminating a negative regulator (Dlk1) did not rescue adipogenesis in Ddx6-KO cells.
  • Human mesenchymal stem cells also require DDX6 for adipocyte maturation.

Conclusions:

  • RNA decay, mediated by Ddx6 and 4E-T, is essential for adipogenesis.
  • The entire transcriptome's RNA decay, not just specific negative regulators, is indispensable for differentiation.
  • Ddx6-dependent RNA decay is conserved across species for adipocyte maturation.