加拿大多伦多病童医院Julie D. Forman-Kay团队发现FMRP和CAPRIN1磷酸化依赖的相分离调控翻译与去腺苷化。该项研究成果发表在2019年8月23日出版的《科学》上。

据了解，参与RNA加工的无膜细胞器是通过相分离组装的生物分子浓缩物。尽管本质无序蛋白区域（IDR）具有重要作用，但IDR相分离的特定相互作用及其功能后果仍然难以捉摸。

为了回答这些问题，研究人员使用了一种最小的浓缩物，这是由两个相互作用的翻译调节因子FMRP和CAPRIN1的C末端无序区形成。FMRP-CAPRIN1浓缩物的核磁共振光谱揭示了涉及富含精氨酸和富芳香区域的相互作用。研究人员发现不同的FMRP丝氨酸/苏氨酸和CAPRIN1酪氨酸磷酸化模式控制RNA的相分离倾向，包括亚区域化，并在体外调节去腺苷酸化和翻译速率。共相分离的残基特异的相互作用表明，磷酸化调节的浓缩物结构和浓缩物内的酶活性对于信号通路的整合如何控制RNA加工和翻译有影响。

附：英文原文

Title: Phospho-dependent phase separation of FMRP and CAPRIN1 recapitulates regulation of translation and deadenylation

Author: Tae Hun Kim, Brian Tsang, Robert M. Vernon, Nahum Sonenberg, Lewis E. Kay, Julie D. Forman-Kay

Issue&Volume: Volume 365 Issue 6455

Abstract: Membraneless organelles involved in RNA processing are biomolecular condensates assembled by phase separation. Despite the important role of intrinsically disordered protein regions (IDRs), the specific interactions underlying IDR phase separation and its functional consequences remain elusive. To address these questions, we used minimal condensates formed from the C-terminal disordered regions of two interacting translational regulators, FMRP and CAPRIN1. Nuclear magnetic resonance spectroscopy of FMRP-CAPRIN1 condensates revealed interactions involving arginine-rich and aromatic-rich regions. We found that different FMRP serine/threonine and CAPRIN1 tyrosine phosphorylation patterns control phase separation propensity with RNA, including subcompartmentalization, and tune deadenylation and translation rates in vitro. The resulting evidence for residue-specific interactions underlying co–phase separation, phosphorylation-modulated condensate architecture, and enzymatic activity within condensates has implications for how the integration of signaling pathways controls RNA processing and translation.

DOI: 10.1126/science.aax4240

Source:https://science.sciencemag.org/content/365/6455/825