Tdrd6a Regulates the Aggregation of Buc into Functional Subcellular Compartments that Drive Germ Cell Specification.

Authors

Roovers EF1, Kaaij LJT1, Redl S1, Bronkhorst AW1, Wiebrands K2, de Jesus Domingues AM1, Huang HY2, Han CT3, Riemer S4, Dosch R4, Salvenmoser W5, Grün D6, Butter F7, van Oudenaarden A2, Ketting RF8.
  1. Biology of Non-coding RNA Group, Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany.
  2. Hubrecht Insitut, Royal Netherlands Academy of Arts and Sciences and  University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
  3. Genomics Core Facility, Institute of Molecular Biology, Ackermannweg 4, 55l28 Mainz, Germany; CeGat GmbH, Center for Genomics and Transcriptomics, Paul-Ehrlich-Straße 23, 72076 Tübingen, Germany.
  4. Institute of Developmental Biochemistry, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
  5. Insitute of Zoology, Center of Molecular Bioscience, University of Innsbruck, Technikerstraße 25, 6020 Innsbruck, Austria.
  6. Hubrecht Institute Royal Netherlands Academy of Arts and Sciences  and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht,the Netherlands; Max Planck Institute of Immunology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
  7. Quantitative Proteomics Group, Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany.
  8. Biology of Non-coding RNA Group, Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany. Electronic address: r.ketting@imb.de

Abstract

Phase separation represents an important form 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 intimately linked phase-separated structures essential for germ cell specification and home to many germ cell-specific mRNAs and proteins. Throughout development, these structures occur as a single large aggregate (Bb), which disperses throughout oogenesis and upon fertilization accumulates again into 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 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 insights into how prion-like protein aggregations can be regulated and highlights the biological relevance of such regulatory events.