TDP-35 sequesters TDP-43 into cytoplasmic inclusions through binding with RNA.
FEBS Lett
; 589(15): 1920-8, 2015 Jul 08.
Article
en En
| MEDLINE
| ID: mdl-26099433
ABSTRACT
TDP-43 (TAR DNA binding protein of 43 kDa) and its C-terminal fragments are thought to be linked to the pathologies of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Here, we demonstrate that the aggregates or inclusions formed by its 35-kDa fragment (namely TDP-35) sequester full-length TDP-43 into cytoplasmic inclusions; and this sequestration is mediated by binding with RNA that is enriched in the cytoplasmic inclusions. RNA recognition motif 1 (RRM1) of TDP-43/TDP-35 plays a dominant role in nucleic-acid binding; mutation in this moiety abrogates formation of the TDP-35 inclusions and its RNA-assisted association with TDP-43. Thus, TDP-35 is able to sequester TDP-43 from nuclear localization into cytoplasmic inclusions, and RNA binding plays an essential role in this process.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
ARN
/
Citoplasma
/
Proteínas de Unión al ADN
Límite:
Humans
Idioma:
En
Revista:
FEBS Lett
Año:
2015
Tipo del documento:
Article
País de afiliación:
China