Spatial proteomic mapping of human nuclear bodies reveals new functional insights into RNA regulation

Abstract

Nuclear bodies are diverse membraneless suborganelles with emerging links to development and disease. Explaining their structure, function, regulation, and implications in human health will require understanding their protein composition; however, isolating nuclear bodies for proteomic analysis remains challenging. We present the first comprehensive proximity proteomics-based map of nuclear bodies, featuring 140 bait proteins (encoded by 119 genes) and 1,816 unique prey proteins. We identified 641 potential nuclear body components, including 131 paraspeckle proteins and 147 nuclear speckle proteins. After validating 31 novel paraspeckle and nuclear speckle components, we discovered regulatory functions for the poorly characterised nuclear speckle- and RNA export-associated proteins PAXBP1, PPIL4, and C19ORF47, and revealed that QKI regulates paraspeckle size. This work provides a systematic framework of nuclear body composition in live cells that will accelerate future research into their organisation and roles in human health and disease.