Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles.
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.
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.
Sven
S
Hennig
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.
Geraldine
G
Kong
Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Taro
T
Mannen
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.
Agata
A
Sadowska
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.
Simon
S
Kobelke
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
Amanda
A
Blythe
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
Gavin J
GJ
Knott
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
K Swaminathan
KS
Iyer
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
Diwei
D
Ho
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia.
Estella A
EA
Newcombe
Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Kana
K
Hosoki
Molecular Profiling Research Center for Drug Discovery, National Institute for Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.
Naoki
N
Goshima
Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Tetsuya
T
Kawaguchi
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia.
Danny
D
Hatters
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.
Laura
L
Trinkle-Mulcahy
Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Tetsuro
T
Hirose
School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
Charles S
CS
Bond
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.
Archa H
AH
Fox
D058227:Amyloidogenic Proteins / Q000737:chemistry; D002467:Cell Nucleus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000502:physiology*; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D060066:Protein Interaction Maps; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
D058227:Amyloidogenic Proteins; D020100:Hydrogels; D047908:Intracellular Signaling Peptides and Proteins; D011328:Prions; C436317:RBM14 protein, human; D016601:RNA-Binding Proteins