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

• Published in: Cell reports (Cambridge) Vol. 42; no. 8; p. 112955
• Main Authors: Jaberi-Lashkari, Nima, Lee, Byron, Aryan, Fardin, Calo, Eliezer
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 29.08.2023; Elsevier
• Subjects: biophysics; condensates; CP: Cell biology; CP: Molecular biology; evolution; low-complexity regions; nucleolus; phase separation; scaffolds; self-assembly; self-assembly; phase separation; scaffolds; CP: Cell biology; low-complexity regions; nucleolus; CP: Molecular biology; condensates; evolution; biophysics
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112955

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. [Display omitted] •TCOF1 is a self-assembling scaffold necessary for the nucleolar fibrillar center (FC)•Self-assembly of TCOF1 requires homotypic interactions between its S/E-rich LCRs•TCOF1 self-assembly is necessary for its ability to scaffold the FC•Human TCOF1 is sufficient to form an FC-like condensate in fish, which lack an FC Jaberi-Lashkari et al. present a model for the evolution of biomolecular condensates by showing that a recently emerged condensate relies on a self-assembling scaffold rather than on many co-interacting scaffolds and that emergence of this single scaffold can explain the emergence of this condensate in the tree of life.