RNA Biology and Innovation, Institute of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Centre for Human Technologies (CHT), Istituto Italiano di Tecnologia (IIT), Via Enrico Melen, 83, 16152, Genova, Italy.
Nat Commun. 2024 Mar 22;15(1):2585. doi: 10.1038/s41467-024-46731-9.
RNA-binding proteins are central for many biological processes and their characterization has demonstrated a broad range of functions as well as a wide spectrum of target structures. RNA G-quadruplexes are important regulatory elements occurring in both coding and non-coding transcripts, yet our knowledge of their structure-based interactions is at present limited. Here, using theoretical predictions and experimental approaches, we show that many chromatin-binding proteins bind to RNA G-quadruplexes, and we classify them based on their RNA G-quadruplex-binding potential. Combining experimental identification of nuclear RNA G-quadruplex-binding proteins with computational approaches, we build a prediction tool that assigns probability score for a nuclear protein to bind RNA G-quadruplexes. We show that predicted G-quadruplex RNA-binding proteins exhibit a high degree of protein disorder and hydrophilicity and suggest involvement in both transcription and phase-separation into membrane-less organelles. Finally, we present the G4-Folded/UNfolded Nuclear Interaction Explorer System (G4-FUNNIES) for estimating RNA G4-binding propensities at http://service.tartaglialab.com/new_submission/G4FUNNIES .
RNA 结合蛋白在许多生物过程中起着核心作用，其特性研究表明它们具有广泛的功能和多样化的靶结构。RNA 四链体是编码和非编码转录本中重要的调节元件，但目前我们对其基于结构的相互作用的了解还很有限。在这里，我们使用理论预测和实验方法表明，许多染色质结合蛋白与 RNA 四链体结合，并根据其与 RNA 四链体结合的潜力对其进行分类。我们将核 RNA 四链体结合蛋白的实验鉴定与计算方法相结合，构建了一个预测工具，该工具可以为核蛋白与 RNA 四链体结合的可能性分配概率评分。我们发现预测的 RNA 四链体结合蛋白具有高度的蛋白质无序性和亲水性，并表明它们参与转录和相分离到无膜细胞器中。最后，我们在 http://service.tartaglialab.com/new_submission/G4FUNNIES 上展示了 RNA G4 结合倾向的估计 RNA G4 结合倾向的 RNA G4 折叠/未折叠核相互作用探索系统（G4-FUNNIES）。
