Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Biophys J. 2024 Jun 4;123(11):1356-1366. doi: 10.1016/j.bpj.2023.07.013. Epub 2023 Jul 21.
DEAD-box helicases are important regulators of biomolecular condensates. However, the mechanisms through which these enzymes affect the dynamics of biomolecular condensates have not been systematically explored. Here, we demonstrate the mechanism by which the mutation of a DEAD-box helicase's catalytic core alters ribonucleoprotein condensate dynamics in the presence of ATP. Through altering RNA length within the system, we are able to attribute the altered biomolecular dynamics and material properties to physical cross-linking of RNA facilitated by the mutant helicase. These results suggest that mutant condensates approach a gel transition when RNA length is increased to lengths comparable to eukaryotic mRNA. Lastly, we show that this cross-linking effect is tunable with ATP concentration, uncovering a system whose RNA mobility and material properties vary with enzyme activity. More generally, these findings point to a fundamental mechanism for modulating condensate dynamics and emergent material properties through nonequilibrium, molecular-scale interactions.
DEAD-box 解旋酶是生物分子凝聚物的重要调节剂。然而，这些酶影响生物分子凝聚物动力学的机制尚未得到系统的探索。在这里，我们展示了在 ATP 存在的情况下，DEAD-box 解旋酶催化核心突变如何改变核糖核蛋白凝聚物的动力学。通过改变系统内的 RNA 长度，我们能够将改变的生物分子动力学和材料特性归因于突变解旋酶促进的 RNA 物理交联。这些结果表明，当 RNA 长度增加到与真核 mRNA 长度相当的长度时，突变凝聚物接近凝胶转变。最后，我们表明，这种交联效应可以通过 ATP 浓度进行调节，揭示了一种其 RNA 迁移率和材料特性随酶活性变化的系统。更一般地说，这些发现指出了通过非平衡、分子尺度相互作用调节凝聚物动力学和新兴材料特性的基本机制。
