An evolutionarily nascent architecture underlying the formation and emergence of biomolecular condensates

Abstract

Biomolecular condensates are implicated in core cellular processes such as gene regulation and ribosome biogenesis. Although the architecture of biomolecular condensates is thought to rely on collective interactions between many components, it is unclear how the collective interactions required for their formation emerge during evolution. Here, we show that the structure and evolution of a recently emerged biomolecular condensate, the nucleolar fibrillar center (FC), is explained by a single self-assembling scaffold, TCOF1. TCOF1 is necessary to form the FC, and it structurally defines the FC through self-assembly mediated by homotypic interactions of serine/glutamate-rich low-complexity regions (LCRs). Finally, introduction of TCOF1 into a species lacking the FC is sufficient to form an FC-like biomolecular condensate. By demonstrating that a recently emerged biomolecular condensate is built on a simple architecture determined by a single self-assembling protein, our work provides a compelling mechanism by which biomolecular condensates can emerge in the tree of life.

Keywords: CP: Cell biology; CP: Molecular biology; biophysics; condensates; evolution; low-complexity regions; nucleolus; phase separation; scaffolds; self-assembly.