Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136.
Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136.
Proc Natl Acad Sci U S A. 2021 Feb 16;118(7). doi: 10.1073/pnas.2014457118.
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.
生物分子凝聚物浓缩分子以促进基本的生化过程，包括转录和 DNA 复制。虽然液态凝聚物被赋予了各种功能，但固态凝聚物通常被认为是无定形的蛋白质储存场所。在这里，我们表明固态的淀粉样体在应激期间协调局部核蛋白合成 (LNPS)。在刺激下，翻译活性核糖体沿着纤维状组装物积累，这些纤维状组装物是淀粉样体的特征。质谱分析鉴定了调节核糖体蛋白和翻译因子，它们从细胞质重新定位到淀粉样体，以维持 LNPS。这些淀粉样的隔室富含新转录的信使 RNA，由热休克因子 1 (HSF1) 富集。应激诱导的核糖体基因间间隔非编码 RNA (rIGSRNA) 的缺失会阻止核蛋白合成机制的招募，从而阻止 LNPS 的发生，并损害核 HSF1 反应。我们提出，淀粉样体在应激期间支持局部核翻译，而固态凝聚物可以促进复杂的生化反应，就像它们的液态对应物一样。
