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Local translation in nuclear condensate amyloid bodies.

Phaedra R TheodoridisMichael BokrosDane MarijanNathan C BalukoffDazhi WangChloe C KirkTaylor D BudineHarris D GoldsmithMiling WangTimothy E AudasStephen Lee
Published in: Proceedings of the National Academy of Sciences of the United States of America (2021)
Biomolecular condensates concentrate molecules to facilitate basic biochemical processes, including transcription and DNA replication. While liquid-like condensates have been ascribed various functions, solid-like condensates are generally thought of as amorphous sites of protein storage. Here, we show that solid-like amyloid bodies coordinate local nuclear protein synthesis (LNPS) during stress. On stimulus, translationally active ribosomes accumulate along fiber-like assemblies that characterize amyloid bodies. Mass spectrometry analysis identified regulatory ribosomal proteins and translation factors that relocalize from the cytoplasm to amyloid bodies to sustain LNPS. These amyloidogenic compartments are enriched in newly transcribed messenger RNA by Heat Shock Factor 1 (HSF1). Depletion of stress-induced ribosomal intergenic spacer noncoding RNA (rIGSRNA) that constructs amyloid bodies prevents recruitment of the nuclear protein synthesis machinery, abolishes LNPS, and impairs the nuclear HSF1 response. We propose that amyloid bodies support local nuclear translation during stress and that solid-like condensates can facilitate complex biochemical reactions as their liquid counterparts can.
Keyphrases
  • heat shock
  • stress induced
  • mass spectrometry
  • heat stress
  • transcription factor
  • high resolution
  • room temperature
  • small molecule
  • tandem mass spectrometry