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

Summary 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.
Graphical Abstract
Highlights • Tdrd6a is required for Bucky ball mobility within aggregates, and for PGC formation • Maternal Tdrd6a coordinates transcript deposition into future PGCs • A dimethylated tri-RG motif in Bucky ball mediates interaction with Tdrd6a • The tri-RG motif is essential for Balbiani body and germ cell formation
Zebrafish Balbiani body and germ plasm are related phase-separated structures. Roovers, Kaaij et al. show that Tdrd6a is required for their formation and mobility through interaction with dimethylated arginines in the prion-like protein Bucky ball, revealing a role for Tudor domain-methylated arginine interactions in in vivo phase separation modulation.