Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles

Sven Hennig, Geraldine Kong, Taro Mannen, Agata Sadowska, Simon Kobelke, Amanda Blythe, Gavin J. Knott, Swaminathan S. Iyer, Diwei Ho, Estella A. Newcombe, Kana Hosoki, Naoki Goshima, Tetsuya Kawaguchi, Danny Hatters, Laura Trinkle-Mulcahy, Tetsuro Hirose, Charles S. Bond, Archa H. Fox

Research output: Contribution to journalArticlepeer-review

224 Citations (Scopus)


Prion-like domains (PLDs) are low complexity sequences found in RNA binding proteins associated with the neurodegenerative disorder amyotrophic lateral sclerosis. Recently, PLDs have been implicated in mediating gene regulation via liquid-phase transitions that drive ribonucleoprotein granule assembly. In this paper, we report many PLDs in proteins associated with paraspeckles, subnuclear bodies that form around long noncoding RNA. We mapped the interactome network of paraspeckle proteins, finding enrichment of PLDs. We show that one protein, RBM14, connects key paraspeckle subcomplexes via interactions mediated by its PLD. We further show that the RBM14 PLD, as well as the PLD of another essential paraspeckle protein, FUS, is required to rescue paraspeckle formation in cells in which their endogenous counterpart has been knocked down. Similar to FUS, the RBM14 PLD also forms hydrogels with amyloid-like properties. These results suggest a role for PLD-mediated liquid-phase transitions in paraspeckle formation, highlighting this nuclear body as an excellent model system for understanding the perturbation of such processes in neurodegeneration.

Original languageEnglish
Pages (from-to)529-539
Number of pages11
JournalThe Journal of Cell Biology
Issue number4
Publication statusPublished - 17 Aug 2015


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