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Tdrd6a regulates the aggregation of Buc into functional subcellular compartments that drive germ cell specification

Elke F. Roovers, Lucas J.T. Kaaij, Stefan Redl, Alfred W. Bronkhorst, Kay Wiebrands, View ORCID ProfileAntónio M. de Jesus Domingues, Hsin-Yi Huang, View ORCID ProfileChung-Ting Han, Willi Salvenmoser, Dominic Grün, View ORCID ProfileFalk Butter, Alexander van Oudenaarden, René F. Ketting
doi: https://doi.org/10.1101/267971
Elke F. Roovers
1Biology of Non-coding RNA Group, Institute of Molecular Biology, Ackermannweg 4, 55128, Mainz, Germany
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Lucas J.T. Kaaij
1Biology of Non-coding RNA Group, Institute of Molecular Biology, Ackermannweg 4, 55128, Mainz, Germany
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Stefan Redl
1Biology of Non-coding RNA Group, Institute of Molecular Biology, Ackermannweg 4, 55128, Mainz, Germany
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Alfred W. Bronkhorst
1Biology of Non-coding RNA Group, Institute of Molecular Biology, Ackermannweg 4, 55128, Mainz, Germany
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Kay Wiebrands
2Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
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António M. de Jesus Domingues
1Biology of Non-coding RNA Group, Institute of Molecular Biology, Ackermannweg 4, 55128, Mainz, Germany
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  • ORCID record for António M. de Jesus Domingues
Hsin-Yi Huang
2Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
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Chung-Ting Han
3Genomics Core Facility, Institute of Molecular Biology, Ackermannweg 4, 55128, Mainz, Germany
4CeGaT GmbH, Center for Genomics and Transcriptomics, Paul-Ehrlich-Straße 23, 72076, Tübingen, Germany
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  • ORCID record for Chung-Ting Han
Willi Salvenmoser
5Institute of Zoology, Center of Molecular Bioscience, University of Innsbruck, Technikerstraβe 25, 6020 Innsbruck, Austria
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Dominic Grün
2Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
6Max Planck Institute of Immunology and Epigenetics, Stübeweg 51, 79108, Freiburg, Germany
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Falk Butter
7Quantitative Proteomics Group, Institute of Molecular Biology, Ackermannweg 4, 55128, Mainz, Germany
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  • ORCID record for Falk Butter
Alexander van Oudenaarden
2Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
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René F. Ketting
1Biology of Non-coding RNA Group, Institute of Molecular Biology, Ackermannweg 4, 55128, Mainz, Germany
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  • For correspondence: r.ketting@imb.de
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Summary

In recent years, it has become clear that phase separation represents an important class of subcellular compartmentalization. However, relatively little is known about how the formation or disassembly of such compartments is regulated. In zebrafish, the Balbiani body (Bb) and the germ plasm (Gp) are phase-separated structures essential for germ cell specification and home to many germ cell-specific mRNAs and proteins. Throughout development, these structures range from a single large aggregate (Bb), to a dispersed state and back to relatively large assemblies (Gp). Formation of the Bb requires Bucky ball (Buc), a protein with prion-like properties. We found that the multi-tudor domain-containing protein Tdrd6a interacts directly with Buc, affecting its mobility and aggregation properties. Importantly, lack of this regulatory interaction leads to significant defects in germ cell development. Our work presents a new mechanism for how prion-like protein-aggregations can be regulated and highlights the biological relevance of such regulatory events.

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Posted February 19, 2018.
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Tdrd6a regulates the aggregation of Buc into functional subcellular compartments that drive germ cell specification
Elke F. Roovers, Lucas J.T. Kaaij, Stefan Redl, Alfred W. Bronkhorst, Kay Wiebrands, António M. de Jesus Domingues, Hsin-Yi Huang, Chung-Ting Han, Willi Salvenmoser, Dominic Grün, Falk Butter, Alexander van Oudenaarden, René F. Ketting
bioRxiv 267971; doi: https://doi.org/10.1101/267971
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Tdrd6a regulates the aggregation of Buc into functional subcellular compartments that drive germ cell specification
Elke F. Roovers, Lucas J.T. Kaaij, Stefan Redl, Alfred W. Bronkhorst, Kay Wiebrands, António M. de Jesus Domingues, Hsin-Yi Huang, Chung-Ting Han, Willi Salvenmoser, Dominic Grün, Falk Butter, Alexander van Oudenaarden, René F. Ketting
bioRxiv 267971; doi: https://doi.org/10.1101/267971

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