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

Abstract

Condensates are biomolecular assemblies that concentrate biomolecules without the help of membranes. They are morphologically highly versatile and may emerge via distinct mechanisms. Nucleic acids–DNA, RNA and poly(ADP-ribose) (PAR) play special roles in the process of condensate organization. These polymeric scaffolds provide multiple specific and nonspecific interactions during nucleation and ‘development’ of macromolecular assemblages. In this review, we focus on condensates formed with PAR. We discuss to what extent the literature supports the phase separation origin of these structures. Special attention is paid to similarities and differences between PAR and RNA in the process of dynamic restructuring of condensates during their functioning.

Regulation of Biomolecular Condensates by Poly(ADP-ribose)

“…The chemical nature of the PAR chain also potently promotes PS: it is a negatively charged multivalent polymer able to bind many PAR readers at once. As previous reviews have noted, ,− PAR is involved in several biological processes that are associated with PS (Figure ). In this section, we will discuss the biophysics of PS, the mechanisms of protein–PAR PS and review the literature that describes the role of PAR in biomolecular condensates.…”

“…An emerging theme is that PAR can serve as a molecular trigger for DNA repair or potentially other stress responses, and as such, PAR can promote the formation of phase-separated granules at specific foci, like a DNA damage site. ,, Therefore, we propose that PAR-mediated interaction can serve as a unifying mechanism for initiating stimulus- or stress-induced granule formation. Such a mechanism has also been suggested by others. ,,− …”

“…Moreover, certain granules, like stress granules (SGs), must only assemble in response to acute stimuli, or cells cannot survive. , Therefore, the cell needs mechanisms to direct the formation of biomolecular condensates on demand. One emerging hypothesis is that a molecule called PAR enables such rapid organization of certain cellular condensates in species that express PARPs. − …”

Length-dependent Intramolecular Coil-to-Globule Transition in Poly(ADP-ribose) Induced by Cations

“…[4][5][6][7][8] PAR may also serve as a scaffold for protein complex or biomolecular condensate formation, where its negative charge allows for multivalent noncovalent interactions with basic proteins. 9,10 In mammalian cells under extreme stress or high doses of DNA-damaging agents, homopolymers with around 200 ADP-ribose units have been observed. 11 However, under normal and mildly stressed conditions, PAR oligomers exhibit a size distribution that ranges from as few as 2 units to approximately 20 units.…”

“…1B) [3][4][5][6][7] . PAR may also serve as a scaffold for protein complex or biomolecular condensate formation, where its negative charge allows for multivalent noncovalent interactions with basic proteins 8,9 .…”