Co-regulation of mRNA translation by TDP-43 and Fragile X Syndrome protein FMRP.
Acta Neuropathol
; 132(5): 721-738, 2016 11.
Article
en En
| MEDLINE
| ID: mdl-27518042
ABSTRACT
For proper mammalian brain development and functioning, the translation of many neuronal mRNAs needs to be repressed without neuronal activity stimulations. We have discovered that the expression of a subclass of neuronal proteins essential for neurodevelopment and neuron plasticity is co-regulated at the translational level by TDP-43 and the Fragile X Syndrome protein FMRP. Using molecular, cellular and imaging approaches, we show that these two RNA-binding proteins (RBP) co-repress the translation initiation of Rac1, Map1b and GluR1 mRNAs, and consequently the hippocampal spinogenesis. The co-repression occurs through binding of TDP-43 to mRNA(s) at specific UG/GU sequences and recruitment of the inhibitory CYFIP1-FMRP complex by its glycine-rich domain. This novel regulatory scenario could be utilized to silence a significant portion of around 160 common target mRNAs of the two RBPs. The study establishes a functional/physical partnership between FMRP and TDP-43 that mechanistically links several neurodevelopmental disorders and neurodegenerative diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biosíntesis de Proteínas
/
ARN Mensajero
/
Proteínas de Unión al ADN
/
Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Acta Neuropathol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Taiwán
Pais de publicación:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY