Predicting dynamic cellular protein-RNA interactions by deep learning using in vivo RNA structures

• 作者: Lei Sun Kui Xu Wenze Huang Yucheng T.Yang Pan Li Lei Tang Tuanlin Xiong Qiangfeng Cliff Zhang
• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2021,（5）
• 所属期刊栏目: ARTICLES
• 页码范围: 495-516
• 页数: 22页
• 语种: 英文

摘要

Interactions with RNA-binding proteins (RBPs) are integral to RNA function and cellular regulation,and dynamically reflect specific cellular conditions.However,presently available tools for predicting RBP-RNA interactions employ RNA sequence and/or predicted RNA structures,and therefore do not capture their condition-dependent nature.Here,after profiling transcriptome-wide in vivo RNA secondary structures in seven cell types,we developed PrismNet,a deep learning tool that integrates experimental in vivo RNA structure data and RBP binding data for matched cells to accurately predict dynamic RBP binding in various cellular conditions.PrismNet results for 168 RBPs support its utility for both understanding CUP-seq results and largely extending such interaction data to accurately analyze additional cell types.Further,PrismNet employs an "attention" strategy to computationally identify exact RBP-binding nucleotides,and we discovered enrichment among dynamic RBP-binding sites for structure-changing variants(riboSNitches),which can link genetic diseases with dysregulated RBP bindings.Our rich profiling data and deep learning-based prediction tool provide access to a previously inaccessible layer of cell-type-specific RBP-RNA interactions,with clear utility for understanding and treating human diseases.