The RNA-binding protein FUS (Fused in Sarcoma) mediates phase separation in biomolecular condensates and functions in transcription by clustering with RNA polymerase II. Specific contact residues and interaction modes formed by FUS and the C-terminal heptad repeats of RNA polymerase II (CTD) have been suggested but not probed directly. Here we show how RGG domains contribute to phase separation with the FUS N-terminal low-complexity domain (SYGQ LC) and RNA polymerase II CTD. Using NMR spectroscopy and molecular simulations, we demonstrate that many residue types, not solely arginine-tyrosine pairs, form condensed-phase contacts via several interaction modes including, but not only sp²-π and cation-π interactions. In phases also containing RNA polymerase II CTD, many residue types form contacts, including both cation-π and hydrogen-bonding interactions formed by the conserved human CTD lysines. Hence, our data suggest a surprisingly broad array of residue types and modes explain co-phase separation of FUS and RNA polymerase II.

RNA 结合蛋白 FUS（肉瘤融合蛋白）介导生物分子凝聚物中的相分离，并通过与 RNA 聚合酶 II 聚集而在转录中发挥作用。FUS 和 RNA 聚合酶 II (CTD) 的 C 端七肽重复序列形成的特定接触残基和相互作用模式已被提出，但尚未直接探讨。在这里，我们展示了 RGG 结构域如何促进 FUS N 末端低复杂性结构域 (SYGQ LC) 和 RNA 聚合酶 II CTD 的相分离。使用核磁共振波谱和分子模拟，我们证明许多残基类型（不仅仅是精氨酸-酪氨酸对）通过多种相互作用模式形成凝聚相接触，包括但不仅限于sp ² - π和阳离子 - π相互作用。在还含有 RNA 聚合酶 II CTD 的相中，许多残基类型形成接触，包括由保守的人 CTD 赖氨酸形成的阳离子π和氢键相互作用。因此，我们的数据表明，一系列令人惊讶的残基类型和模式可以解释 FUS 和 RNA 聚合酶 II 的共相分离。