RBPtool: A Deep Language Model Framework for Multi-Resolution RBP-RNA Binding Prediction and RNA Molecule Design

Jiyue Jiang, Yitao Xu, Zikang Wang, Yihan Ye, Yanruisheng Shao, Yuheng Shan, Jiuming Wang, Xiaodan Fan, Jiao Yuan, Yu Li


Abstract
RNA-binding proteins (RBPs) play essential roles in post-transcriptional gene regulation via recognizing specific RNA molecules as well as modulating several key physiological processes in cellulo, represented by alternative splicing and RNA degradation. Despite extensive research, most existing approaches still rely on superficial sequence features or coarse structural representations, limiting their ability to capture the intricate nature of RBP-RNA interactions. The recent surge in large language models (LLMs), combined with advances in geometric deep learning for extracting three-dimensional representations, enables the integration of multi-modal, multi-scale biological data for precise modeling and biologically informed de novo RNA design. In this work, we curate and extend RPI15223 into a multi-resolution, structure-level RBP-RNA dataset, and introduce RBPtool, a multi-task, multi-resolution framework that combines a geometric vector perception (GVP) module together with a deep language model encoder to fuse sequence and structural information. Our tool achieves state-of-the-art performance on public benchmarks and the RPI15223 dataset, while also supporting fine-grained level predictions and enabling de novo RNA design through a generative module conditioned on protein, cell-type, and specified species. RBPtool provides a fast and versatile platform for both fundamental RBP-RNA research and practical RNA drug design, delivering enhanced predictive accuracy and fine-grained structural insights.
Anthology ID:
2025.emnlp-main.110
Volume:
Proceedings of the 2025 Conference on Empirical Methods in Natural Language Processing
Month:
November
Year:
2025
Address:
Suzhou, China
Editors:
Christos Christodoulopoulos, Tanmoy Chakraborty, Carolyn Rose, Violet Peng
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EMNLP
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Publisher:
Association for Computational Linguistics
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Pages:
2170–2185
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Cite (ACL):
Jiyue Jiang, Yitao Xu, Zikang Wang, Yihan Ye, Yanruisheng Shao, Yuheng Shan, Jiuming Wang, Xiaodan Fan, Jiao Yuan, and Yu Li. 2025. RBPtool: A Deep Language Model Framework for Multi-Resolution RBP-RNA Binding Prediction and RNA Molecule Design. In Proceedings of the 2025 Conference on Empirical Methods in Natural Language Processing, pages 2170–2185, Suzhou, China. Association for Computational Linguistics.
Cite (Informal):
RBPtool: A Deep Language Model Framework for Multi-Resolution RBP-RNA Binding Prediction and RNA Molecule Design (Jiang et al., EMNLP 2025)
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