Seim Ian, Zhang Vita, Jalihal Ameya P, Stormo Benjamin M, Cole Sierra J, Ekena Joanne, Nguyen Hung T, Thirumalai D, Gladfelter Amy S
Duke University, Department of Cell Biology, Durham, NC.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
bioRxiv. 2024 Dec 12:2024.12.11.627970. doi: 10.1101/2024.12.11.627970.
Most amino acids are encoded by multiple codons, making the genetic code degenerate. Synonymous mutations affect protein translation and folding, but their impact on RNA itself is often neglected. We developed a genetic algorithm that introduces synonymous mutations to control the diversity of structures sampled by an mRNA. The behavior of the designed mRNAs reveals a physical code layered in the genetic code. We find that mRNA conformational heterogeneity directs physical properties and functional outputs of RNA-protein complexes and biomolecular condensates. The role of structure and disorder of proteins in biomolecular condensates is well appreciated, but we find that RNA conformational heterogeneity is equally important. This feature of RNA enables both evolution and engineers to build cellular structures with specific material and responsive properties.
大多数氨基酸由多个密码子编码，这使得遗传密码具有简并性。同义突变会影响蛋白质的翻译和折叠，但其对RNA本身的影响往往被忽视。我们开发了一种遗传算法，通过引入同义突变来控制mRNA所采样结构的多样性。设计的mRNA的行为揭示了遗传密码中分层的物理密码。我们发现，mRNA构象异质性指导RNA-蛋白质复合物和生物分子凝聚物的物理性质和功能输出。蛋白质的结构和无序在生物分子凝聚物中的作用已得到充分认识，但我们发现RNA构象异质性同样重要。RNA的这一特性使进化和工程师都能够构建具有特定材料和响应特性的细胞结构。
