Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5
| Autor: | Maike Getwan, Hiroshi Hamada, Jose L Pelliccia, Antonio J. Giraldez, Jason C. McSheene, Axel Schweickert, Michael D. Sheets, Melanie Tingler, Megan E. Dowdle, Philipp Vick, Charles E. Vejnar, Rebecca D. Burdine, Markus Maerker, Katsura Minegishi, Valeria Yartseva, Danielle S Hamilton, Martin Blum, Vanessa Gonzalez |
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| Přispěvatelé: | University of Zurich, Schweickert, Axel |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Untranslated region
Ribonuclease III 10017 Institute of Anatomy RNA Stability Science Xenopus General Physics and Astronomy Embryonic Development RNA-binding protein 610 Medicine & health 1600 General Chemistry RNA decay General Biochemistry Genetics and Molecular Biology Article Mice Xenopus laevis 1300 General Biochemistry Genetics and Molecular Biology Animals Post-transcriptional regulation 3' Untranslated Regions Zebrafish Body Patterning Messenger RNA Multidisciplinary biology Chemistry Lateral plate mesoderm Gene Expression Regulation Developmental RNA-Binding Proteins General Chemistry biology.organism_classification 3100 General Physics and Astronomy Cell biology Embryonic induction biology.protein Intercellular Signaling Peptides and Proteins 570 Life sciences NODAL Dicer Cell signalling |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Nature Communications |
| DOI: | 10.5167/uzh-208861 |
| Popis: | Rotating cilia at the vertebrate left-right organizer (LRO) generate an asymmetric leftward flow, which is sensed by cells at the left LRO margin. Ciliary activity of the calcium channel Pkd2 is crucial for flow sensing. How this flow signal is further processed and relayed to the laterality-determining Nodal cascade in the left lateral plate mesoderm (LPM) is largely unknown. We previously showed that flow down-regulates mRNA expression of the Nodal inhibitor Dand5 in left sensory cells. De-repression of the co-expressed Nodal, complexed with the TGFß growth factor Gdf3, drives LPM Nodal cascade induction. Here, we show that post-transcriptional repression of dand5 is a central process in symmetry breaking of Xenopus, zebrafish and mouse. The RNA binding protein Bicc1 was identified as a post-transcriptional regulator of dand5 and gdf3 via their 3′-UTRs. Two distinct Bicc1 functions on dand5 mRNA were observed at pre- and post-flow stages, affecting mRNA stability or flow induced translational inhibition, respectively. To repress dand5, Bicc1 co-operates with Dicer1, placing both proteins in the process of flow sensing. Intriguingly, Bicc1 mediated translational repression of a dand5 3′-UTR mRNA reporter was responsive to pkd2, suggesting that a flow induced Pkd2 signal triggers Bicc1 mediated dand5 inhibition during symmetry breakage. The authors show that post-transcriptional regulation of the cilia-driven leftward flow target dand5 is central to symmetry breakage in frog, fish and mouse and is mediated by a 139 nt Bicc1 responsive element in the dand5 3′UTR, and they present evidence that Pkd2 regulates this Bicc1/dand5 module. |
| Databáze: | OpenAIRE |
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