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Fluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA

Katsura Minegishi1, Benjamin Rothé2, Kaoru R Komatsu3

  • 1Laboratory for Organismal Patterning, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan.

Nature Communications
|July 2, 2021
PubMed

Insights

Mouse embryo left-right asymmetry depends on sensing fluid flow. Leftward flow triggers calcium currents, activating proteins that degrade Dand5 mRNA specifically on the left side.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Left-right (L-R) asymmetry in mouse embryos is crucial for organ positioning.
  • This asymmetry is established at the node through sensing of leftward fluid flow by immotile cilia.

Purpose of the Study:

  • To investigate the molecular mechanisms by which fluid flow induces Dand5 mRNA decay.
  • To identify the specific mRNA regions and proteins involved in this directional degradation.

Main Methods:

  • Analysis of Dand5 mRNA 3' untranslated region (3'-UTR) function using reporter transgenes.
  • Investigating the roles of calcium (Ca2+), Pkd2, Bicc1, and Cnot3 in mRNA decay.
  • Identifying Bicc1 binding sequences within the Dand5 3'-UTR.

Main Results:

  • The first 200 nucleotides of the Dand5 3'-UTR are necessary and sufficient for left-sided decay.
  • Bicc1 binds to a conserved GACGUGAC motif in the Dand5 3'-UTR.
  • Cnot3 interacts with Bicc1 and is essential for Dand5 mRNA decay at the node.

Conclusions:

  • Leftward fluid flow induces Ca2+ currents that activate Bicc1 and Ccr4-Not.
  • This activation leads to the specific degradation of Dand5 mRNA on the left side of the node.
  • The findings elucidate a key mechanism in establishing molecular L-R asymmetry.

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