Poly(ADP-ribose) drives condensation of FUS via a transient interaction

A sePARate phase? Poly(ADP-ribose) versus RNA in the organization of biomolecular condensates

“…FUS can likewise use long PAR polymers (e.g. >16 monomers) as a scaffold for multivalent interactions that drive condensation, as it has been described for FUS and RNA ( 60 ).…”

“…Interestingly, PAR is able to induce FUS condensation in a completely different manner via a trans -acting catalyst-like mechanism ( 60 ) (see Figure 2 ). According to this mechanism, PAR chains of all lengths (>4 monomers) can alter FUS into LLPS-prone form via transient interactions.…”

“…According to this mechanism, PAR chains of all lengths (>4 monomers) can alter FUS into LLPS-prone form via transient interactions. The primed FUS is able to trigger the formation and maintain FUS condensates on its own (without PAR) ( 60 ). Thus, FUS droplets remain intact after treatment of FUS-PAR condensates by PAR-degrading enzyme PARG.…”

“…Moreover, the PAR-free fraction of PAR-treated FUS recruited unreacted FUS molecules into a condensate ( 60 ). A strikingly low concentration of PAR (1 nM) was sufficient to induce FUS condensation; interestingly, this value is three orders of magnitude lower than in the case of RNA ( 60 ), and is manifoldly lower than the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$K_{d_{app}}$\end{document} (>200 nM) for PAR–FUS binding. Stimulation of FUS aggregation in vitro by sub-stoichiometric amounts of PAR was also demonstrated previously ( 5 ).…”

Modulating liquid–liquid phase separation of FUS: mechanisms and strategies

“…In this case, PAR runs a length-dependent catalyst-like mechanism that PAR chains with lengths comparable to those of RNA show one thousand times higher potency for promoting condensation than RNA in vitro . 106…”