Arginine-Enriched Mixed-Charge Domains Provide Cohesion for Nuclear Speckle Condensation.
Mol Cell
; 77(6): 1237-1250.e4, 2020 03 19.
Article
en En
| MEDLINE
| ID: mdl-32048997
ABSTRACT
Low-complexity protein domains promote the formation of various biomolecular condensates. However, in many cases, the precise sequence features governing condensate formation and identity remain unclear. Here, we investigate the role of intrinsically disordered mixed-charge domains (MCDs) in nuclear speckle condensation. Proteins composed exclusively of arginine-aspartic acid dipeptide repeats undergo length-dependent condensation and speckle incorporation. Substituting arginine with lysine in synthetic and natural speckle-associated MCDs abolishes these activities, identifying a key role for multivalent contacts through arginine's guanidinium ion. MCDs can synergize with a speckle-associated RNA recognition motif to promote speckle specificity and residence. MCD behavior is tunable through net-charge increasing negative charge abolishes condensation and speckle incorporation. Contrastingly, increasing positive charge through arginine leads to enhanced condensation, speckle enlargement, decreased splicing factor mobility, and defective mRNA export. Together, these results identify key sequence determinants of MCD-promoted speckle condensation and link the dynamic material properties of speckles with function in mRNA processing.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Arginina
/
ARN Mensajero
/
Núcleo Celular
/
Empalme del ARN
/
Proteínas Intrínsecamente Desordenadas
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Factores de Empalme Serina-Arginina
/
Lisina
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article
País de afiliación:
Singapur