<p>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 <i>C9ORF72</i>-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.</p>

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

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

摘要

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.