Journal Article

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

Komatsu, Kaoru R., Nishimura, Hiromi, Bando, Kana, Ono, Hiroki, Yamamoto, Tadashi, Minegishi, Katsura, Hamada, Hiroshi, Sai, Xiaorei, Katoh, Takanobu A., Takaoka, Katsuyoshi, Rothé, Benjamin, Saito, Hirohide, Kiyonari, Hiroshi, Constam, Daniel B., Ikawa, Yayoi, Kajikawa, Eriko, Miyashita, Emi

2021

Overview

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 2+ , 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 2+ currents induced by leftward fluid flow stimulate Bicc1 and Ccr4-Not to mediate Dand5 mRNA degradation specifically on the left side of the node. Questioning what regulates left-right asymmetry breaking in the mouse node: the authors identify a 200 bp stretch of the Dand5 3’UTR where Bicc1 binds, and Cnot proteins downstream of calcium flow regulate the post-transcriptional regulation of Dand5 by Bicc1.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 3' Untranslated Regions / 38 / 631/136/1455 / 631/136/1660/1993 / 631/337/1645/2020 / 631/80/86/1999 / Animals / Asymmetry / Calcium currents / Calcium ions / Cilia / Decay / Degradation / Embryo, Mammalian - metabolism / Embryos / Fluid dynamics / Fluid flow / Gene Expression Regulation, Developmental / Gene regulation / Humanities and Social Sciences / Intercellular Signaling Peptides and Proteins - genetics / Intercellular Signaling Peptides and Proteins - metabolism / Ion channels / Laboratories / Mice / Mice, Knockout / mRNA turnover / multidisciplinary / Nodes / Nucleotides / Post-transcription / Proteins / Receptors, CCR4 - genetics / Receptors, CCR4 - metabolism / RNA Stability - physiology / RNA, Messenger - metabolism / RNA-binding protein / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Science / Science (multidisciplinary) / Symmetry / Transcription Factors / TRPP Cation Channels - metabolism