A framework for the exploration of subcellular compartmentalization of RNA-binding proteins

The ability of RNA-binding proteins to form complexes with other biomolecules underpins a broad range of structural properties and functions. Understanding the subcellular distribution of RNA-binding proteins and their interacting partners in the steady state and upon perturbation can therefore shed light on these aspects. Here, we present the compartmentalized RNA-Binding Protein (or coRBP) map, an experimental resource and analytical pipeline to study subcellular RNA-binding proteins through multimodal dataset integration and machine learning. Using this approach, we generate a dataset of 1,768 known and putative RNA-binding proteins distributed in a broad panel of subcellular compartments and delineate their intermolecular and intercompartmental relationships. We also establish a hierarchy of RNA-binding protein-containing complexes at multiple scales across the cell, which suggests additional functions for multiple RNA-binding proteins. Furthermore, we investigate changes in RNA-binding protein complex composition and subcellular distribution in response to C9ORF72-associated amyotrophic lateral sclerosis/frontotemporal dementia dipeptide repeats and DNA damage stress. The coRBP map provides a resource to study the roles of RNA-binding proteins in homeostasis and disease.

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Publication Details

Journal
Nature Communications
Published
2026-04-21
DOI
https://doi.org/10.1038/s41467-026-71511-y
Primary Topic
RNA Research and Splicing
Type
article
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article

A framework for the exploration of subcellular compartmentalization of RNA-binding proteins

Giacomo Volpe, Jan Mulder, Miguel A. Esteban, Maria Pia Cosma et al.
Nature Communications
RNA Research and Splicing
article

A framework for the exploration of subcellular compartmentalization of RNA-binding proteins

Giacomo Volpe, Jan Mulder, Miguel A. Esteban, Maria Pia Cosma, Yiwei Lai, Álvaro Castells-García, Chuanyu Liu, Yuan Lv, Patrick H. Maxwell, Bin Peng, Shahzina Kanwal, Mingwei Sun, Xingzhi Xu, Andrew P. Hutchins, Xiangpeng Guo, Dongye Wang, Xiyuan Zheng, Jieyi Hu, Francesca Aguiló, Tao Yang, Jingjing Wang, Aiping Wang, Jingxia Zheng, Liang Wu, Muqddas Tariq, Md. Abdul Mazid, Jianwen Yuan, Luciano Di Croce, Emma Lundberg, M Jiang, Yuanyuan Lu, Xiaofeng Wei, Dajiang Qin
article en

Abstract

The ability of RNA-binding proteins to form complexes with other biomolecules underpins a broad range of structural properties and functions. Understanding the subcellular distribution of RNA-binding proteins and their interacting partners in the steady state and upon perturbation can therefore shed light on these aspects. Here, we present the compartmentalized RNA-Binding Protein (or coRBP) map, an experimental resource and analytical pipeline to study subcellular RNA-binding proteins through multimodal dataset integration and machine learning. Using this approach, we generate a dataset of 1,768 known and putative RNA-binding proteins distributed in a broad panel of subcellular compartments and delineate their intermolecular and intercompartmental relationships. We also establish a hierarchy of RNA-binding protein-containing complexes at multiple scales across the cell, which suggests additional functions for multiple RNA-binding proteins. Furthermore, we investigate changes in RNA-binding protein complex composition and subcellular distribution in response to C9ORF72-associated amyotrophic lateral sclerosis/frontotemporal dementia dipeptide repeats and DNA damage stress. The coRBP map provides a resource to study the roles of RNA-binding proteins in homeostasis and disease.

Nature Communications
BGI Group (China) (CN), Institució Catalana de Recerca i Estudis Avançats (ES), Guangdong University of Technology (CN), Anhui University (CN), Xinjiang Medical University (CN), Universitat Pompeu Fabra (ES), Shanxi Medical University (CN), Jilin University (CN), Chinese Academy of Sciences (CN), University of Cambridge (GB), Science for Life Laboratory (SE), Fifth Affiliated Hospital of Xinjiang Medical University (CN), Guangzhou Institutes of Biomedicine and Health (CN), Hefei Institutes of Physical Science (CN), Karolinska Institutet (SE), Southern University of Science and Technology (CN), Fahd bin Sultan University (SA), Wuhan University (CN), Shenzhen Bay Laboratory (CN), Guangzhou Regenerative Medicine and Health Guangdong Laboratory (CN), State Key Laboratory of Plant Genomics (CN), Istituto Tumori Bari (IT), Centre for Genomic Regulation (ES), Shenzhen University Health Science Center (CN), Guangdong Academy of Medical Sciences (CN), China National GeneBank (CN), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Guangdong Provincial People's Hospital (CN), Guangzhou Eighth People's Hospital (CN), University of Chinese Academy of Sciences (CN), BGI Research (CN), Southern Medical University (CN), KTH Royal Institute of Technology (SE), University of Hong Kong (HK), Umeå University (SE), Guangzhou Medical University (CN), Stanford University (US)
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RNA Research and Splicing
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