Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles.
J Cell Biol
; 210(4): 529-39, 2015 Aug 17.
Article
em En
| MEDLINE
| ID: mdl-26283796
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Príons
/
Núcleo Celular
/
Proteínas de Ligação a RNA
/
Peptídeos e Proteínas de Sinalização Intracelular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Austrália