PhaseCat · Protein-RNA phase-separated condensates and their capacity for catalysis (PhaseCat)

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Project objective

The debate of how life has evolved and which biomolecules (DNA, RNA and/or proteins) came first is still ongoing. What is clear is thatRNA and proteins must have closely co-evolved, considering their essential interactions in the cell e.g. in the ribosome, an ancientprotein-RNA complex indispensable for protein production in all cells. The ribosome catalyses two key reactions: aminolysis, wherepeptide bonds are formed, and peptidyl hydrolysis, where the complete protein is released after translation. Both reactions occur atthe peptidyl-transferase centre, the active site composed of RNA. On the other hand, an enormous variety of reactions are catalysedby the enzymatic activity of peptides and proteins. Given their evolutionary co-occurrence, it is likely that the catalytic capabilities ofproteins and RNA originally co-evolved. Importantly, proteins and RNA can form phase-separated condensates (PSCs), membranelessorganelles that perform key functions in present-day cells. As PSCs form spontaneously, this raises the possibility that they werefunctional in the primordial soup as well. This idea is especially compelling because PSCs can, due to increased molecularconcentrations, enhance catalytic capacity. In PhaseCat, we address how such protein-RNA catalytic reactions may have evolved inPSCs, especially in the context of primordial translation, and how they could be exploited for industrially relevant reactions. Thecombination of fundamental and applied research forms an ideal training ground for doctoral students, who will be trained tounderstand protein-RNA interactions leading to phase separation, a central biological mechanism with exploitation potential.PhaseCat integrates high-throughput screening of PSCs through microfluidics combined with Raman spectroscopy, analysis ofbiological catalysis by proteins/RNA and its application in green chemistry, and computational methods to tie together allcomponents, predict properties and inform experiment.

Original text from CORDIS.

Participants

• VRIJE UNIVERSITEIT BRUSSEL · Bruxelles / BrusselCoordinatorBelgium
• MICROFLUIDICS INNOVATION CENTER · PARISFrance
• PUXANO BV · GentBelgium
• SOLFARCOS SOLUCOES FARMACEUTICAS E COSMETICAS LDA · BRAGAPortugal
• SPECTROMETRY VISION BV · ALMERENetherlands
• UNIVERSIDADE NOVA DE LISBOA · LisboaPortugal
• UNIVERSITAT WIEN · WienAustria

Links

• View on CORDIS
• DOI: 10.3030/101312146