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J Cell Biol. 2015 Aug 17;210(4):529-39. doi: 10.1083/jcb.201504117.

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

Author information

1
The Harry Perkins Institute of Medical Research, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia The Centre for Medical Research, The University of Western Australia, Crawley, WA 6009, Australia.
2
Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
3
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
4
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia.
5
Molecular Profiling Research Center for Drug Discovery, National Institute for Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.
6
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5.
7
The Harry Perkins Institute of Medical Research, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia The Centre for Medical Research, The University of Western Australia, Crawley, WA 6009, Australia archa.fox@uwa.edu.au.

Abstract

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.

PMID:
26283796
PMCID:
PMC4539981
DOI:
10.1083/jcb.201504117
[Indexed for MEDLINE]
Free PMC Article

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