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

Sven Hennig, Geraldine Kong, T. Mannen, Agata Sadowska, Simon Kobelke, Amanda Blythe, G.J. Knott, Killugudi Swaminatha Iyer, D. Ho, E.A. Newcombe, K. Hosoki, N. Goshima, T. Kawaguchi, D. Hatters, L. Trinkle-Mulcahy, T. Hirose, Charlie Bond, Archa Fox

Research output: Contribution to journalArticle

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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.
Original languageEnglish
Pages (from-to)529-539
JournalThe Journal of Cell Biology
Volume210
Issue number4
DOIs
Publication statusPublished - 17 Aug 2015

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Prions
Phase Transition
RNA-Binding Protein FUS
Long Noncoding RNA
RNA Recognition Motif Proteins
Hydrogels
Ribonucleoproteins
RNA-Binding Proteins
Amyotrophic Lateral Sclerosis
Amyloid
Neurodegenerative Diseases
Proteins

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Hennig, Sven ; Kong, Geraldine ; Mannen, T. ; Sadowska, Agata ; Kobelke, Simon ; Blythe, Amanda ; Knott, G.J. ; Swaminatha Iyer, Killugudi ; Ho, D. ; Newcombe, E.A. ; Hosoki, K. ; Goshima, N. ; Kawaguchi, T. ; Hatters, D. ; Trinkle-Mulcahy, L. ; Hirose, T. ; Bond, Charlie ; Fox, Archa. / Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles. In: The Journal of Cell Biology. 2015 ; Vol. 210, No. 4. pp. 529-539.
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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.",
author = "Sven Hennig and Geraldine Kong and T. Mannen and Agata Sadowska and Simon Kobelke and Amanda Blythe and G.J. Knott and {Swaminatha Iyer}, Killugudi and D. Ho and E.A. Newcombe and K. Hosoki and N. Goshima and T. Kawaguchi and D. Hatters and L. Trinkle-Mulcahy and T. Hirose and Charlie Bond and Archa Fox",
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Hennig, S, Kong, G, Mannen, T, Sadowska, A, Kobelke, S, Blythe, A, Knott, GJ, Swaminatha Iyer, K, Ho, D, Newcombe, EA, Hosoki, K, Goshima, N, Kawaguchi, T, Hatters, D, Trinkle-Mulcahy, L, Hirose, T, Bond, C & Fox, A 2015, 'Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles' The Journal of Cell Biology, vol. 210, no. 4, pp. 529-539. https://doi.org/10.1083/jcb.201504117

Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles. / Hennig, Sven; Kong, Geraldine; Mannen, T.; Sadowska, Agata; Kobelke, Simon; Blythe, Amanda; Knott, G.J.; Swaminatha Iyer, Killugudi; Ho, D.; Newcombe, E.A.; Hosoki, K.; Goshima, N.; Kawaguchi, T.; Hatters, D.; Trinkle-Mulcahy, L.; Hirose, T.; Bond, Charlie; Fox, Archa.

In: The Journal of Cell Biology, Vol. 210, No. 4, 17.08.2015, p. 529-539.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles

AU - Hennig, Sven

AU - Kong, Geraldine

AU - Mannen, T.

AU - Sadowska, Agata

AU - Kobelke, Simon

AU - Blythe, Amanda

AU - Knott, G.J.

AU - Swaminatha Iyer, Killugudi

AU - Ho, D.

AU - Newcombe, E.A.

AU - Hosoki, K.

AU - Goshima, N.

AU - Kawaguchi, T.

AU - Hatters, D.

AU - Trinkle-Mulcahy, L.

AU - Hirose, T.

AU - Bond, Charlie

AU - Fox, Archa

PY - 2015/8/17

Y1 - 2015/8/17

N2 - 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.

AB - 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.

U2 - 10.1083/jcb.201504117

DO - 10.1083/jcb.201504117

M3 - Article

VL - 210

SP - 529

EP - 539

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 4

ER -