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流体流动诱导的小鼠胚胎中 Dand5 mRNA 的左右不对称衰减需要 Bicc1-Ccr4 RNA 降解复合物。

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

机构信息

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

Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Life Sciences, Lausanne, Switzerland.

出版信息

Nat Commun. 2021 Jul 1;12(1):4071. doi: 10.1038/s41467-021-24295-2.

DOI:10.1038/s41467-021-24295-2
PMID:34210974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8249388/
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.

摘要

分子左右（L-R）不对称性是在小鼠胚胎的节点处建立的，这是由于不动纤毛的 peri-nodal 冠细胞对左侧的流体流动的感应，以及随之而来的 Dand5 mRNA 在左侧的降解。我们在这里研究了流体流动如何诱导 Dand5 mRNA 衰减。我们发现 Dand5 mRNA 3'非翻译区（3'-UTR）的前 200 个核苷酸对于左侧衰减和介导 3'-UTR 报告基因转染体对 Ca、阳离子通道 Pkd2、RNA 结合蛋白 Bicc1 及其对流动方向的调节的反应是必要和充分的。我们表明，Bicc1 优先识别 GACR 和 YGAC 序列，这可以解释其与位于近端 Dand5 3'-UTR 中的保守 GACGUGAC 基序的特异性结合。Ccr4-Not 去腺苷酸酶复合物的 Cnot3 成分与 Bicc1 相互作用，对于节点处的 Dand5 mRNA 衰减也是必需的。这些结果表明，由左侧流体流动诱导的 Ca 电流刺激 Bicc1 和 Ccr4-Not 来介导 Dand5 mRNA 特异性降解节点的左侧。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/4b00f6918d60/41467_2021_24295_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/2d48112802e1/41467_2021_24295_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/ad079850ab7a/41467_2021_24295_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/a057cb9cea50/41467_2021_24295_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/19e0d5f603b7/41467_2021_24295_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/583a919152d4/41467_2021_24295_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/787e92fe6d86/41467_2021_24295_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/4f959d8bba07/41467_2021_24295_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/483c8930b155/41467_2021_24295_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/4b00f6918d60/41467_2021_24295_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/2d48112802e1/41467_2021_24295_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/ad079850ab7a/41467_2021_24295_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/a057cb9cea50/41467_2021_24295_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/19e0d5f603b7/41467_2021_24295_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/583a919152d4/41467_2021_24295_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/787e92fe6d86/41467_2021_24295_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/4f959d8bba07/41467_2021_24295_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/483c8930b155/41467_2021_24295_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6037/8249388/4b00f6918d60/41467_2021_24295_Fig9_HTML.jpg

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