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Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions
Nature Materials ( IF 37.2 ) Pub Date : 2017-11-06 , DOI: 10.1038/nmat5006
Hideki Nakamura , Albert A. Lee , Ali Sobhi Afshar , Shigeki Watanabe , Elmer Rho , Shiva Razavi , Allister Suarez , Yu-Chun Lin , Makoto Tanigawa , Brian Huang , Robert DeRose , Diana Bobb , William Hong , Sandra B. Gabelli , John Goutsias , Takanari Inoue

Some protein components of intracellular non-membrane-bound entities, such as RNA granules, are known to form hydrogels in vitro. The physico-chemical properties and functional role of these intracellular hydrogels are difficult to study, primarily due to technical challenges in probing these materials in situ. Here, we present iPOLYMER, a strategy for a rapid induction of protein-based hydrogels inside living cells that explores the chemically inducible dimerization paradigm. Biochemical and biophysical characterizations aided by computational modelling show that the polymer network formed in the cytosol resembles a physiological hydrogel-like entity that acts as a size-dependent molecular sieve. We functionalize these polymers with RNA-binding motifs that sequester polyadenine-containing nucleotides to synthetically mimic RNA granules. These results show that iPOLYMER can be used to synthetically reconstitute the nucleation of biologically functional entities, including RNA granules in intact cells.

中文翻译:

通过多价分子相互作用在细胞内生产水凝胶和合成RNA颗粒

已知细胞内非膜结合实体的某些蛋白质成分(例如RNA颗粒)会在体外形成水凝胶。这些细胞内水凝胶的物理化学性质和功能作用很难研究,主要是由于原位探测这些材料的技术挑战。在这里,我们介绍iPOLYMER,这是一种在活细胞内快速诱导基于蛋白质的水凝胶的策略,该策略探索了化学诱导的二聚化范式。通过计算模型进行的生物化学和生物物理表征表明,在胞质溶胶中形成的聚合物网络类似于生理水凝胶状实体,可作为尺寸依赖性分子筛。我们将这些聚合物与RNA结合基序功能化,这些基序将含聚腺嘌呤的核苷酸隔离到合成模拟的RNA颗粒中。这些结果表明,iPOLYMER可用于合成重建完整细胞中生物学功能实体(包括RNA颗粒)的成核。
更新日期:2017-11-06
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