AI Article Synopsis

  • - The study focuses on how leftward fluid flow in the mouse embryo's node influences the breakdown of Dand5 mRNA, crucial for establishing left-right asymmetry during development.
  • - It was found that the first 200 nucleotides of Dand5's 3' untranslated region (3'-UTR) are essential for its left-sided degradation, responding to factors like Ca ions, the cation channel Pkd2, and the RNA-binding protein Bicc1.
  • - Bicc1 interacts with specific RNA sequences and works with the Cnot3 component of the Ccr4-Not deadenylase complex to facilitate left-sided Dand5 mRNA decay when prompted by fluid flow.

Article Abstract

Molecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examined how the fluid flow induces Dand5 mRNA decay. We found that the first 200 nucleotides in the 3' untranslated region (3'-UTR) of Dand5 mRNA are necessary and sufficient for the left-sided decay and to mediate the response of a 3'-UTR reporter transgene to Ca, the cation channel Pkd2, the RNA-binding protein Bicc1 and their regulation by the flow direction. We show that Bicc1 preferentially recognizes GACR and YGAC sequences, which can explain the specific binding to a conserved GACGUGAC motif located in the proximal Dand5 3'-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required for Dand5 mRNA decay at the node. These results suggest that Ca currents induced by leftward fluid flow stimulate Bicc1 and Ccr4-Not to mediate Dand5 mRNA degradation specifically on the left side of the node.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249388PMC
http://dx.doi.org/10.1038/s41467-021-24295-2DOI Listing

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