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SUMMARY:RNA encodes condensate material properties - Amy Gladfelter (Duke 
 University)
DTSTART:20231010T080000Z
DTEND:20231010T084000Z
UID:TALK204781@talks.cam.ac.uk
DESCRIPTION:Biomolecular condensates are membrane-free compartments that s
 patially and temporally organize biochemistry in cells. Nucleic acids are 
 frequence drivers and architectural elements in condensates however the mo
 lecular grammar that dictates the composition and physical states of conde
 nsates remains mysterious.&nbsp\; To examine how RNA sequence and structur
 e impact the form and function of condensates\, we created an evolutionary
  algorithm that designs shuffled mRNA sequences which maximize or minimize
  predicted free energies of folding while preserving mass\, known protein 
 binding sites\, encoded amino acid sequence\, and nucleotide composition. 
 RNAs with minimized free energies of folding contain many stable duplexes\
 , while RNAs with maximized energies have unstable structures and long sin
 gle-stranded regions. Using mass photometry\, we show that RNAs with stabl
 e structures are mostly monomeric\, while RNAs with unstable structures ca
 n multimerize. When mixed with protein\, these differential RNA-RNA intera
 ctions affect dense phase compositions. Specifically\, unstable RNAs form 
 condensates with high RNA and low protein concentrations\, while the conve
 rse is true for RNAs with stable structures. Using microbead rheology\, we
  observe that unstable RNAs form condensates with long viscoelastic relaxa
 tion times that increase with condensate age\, indicating elastic properti
 es at many timescales. By contrast\, stable RNAs form less elastic condens
 ates with shorter relaxation times that increase to a lesser degree with t
 ime. These properties are recapitulated in non-equilibrium conditions in l
 iving cells. We hypothesize that such aging is controlled by the exchange 
 of intra- for inter-molecular base pairing among RNAs whose folding free e
 nergies determine the timescale of such exchanges. Thus\, RNA structure ca
 n have multi-scale consequences for biomolecular condensates\, with impact
 s on condensate composition and material properties.
LOCATION:Seminar Room 1\, Newton Institute
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