FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment.
EMBO J
; 31(24): 4502-10, 2012 Dec 12.
Article
em En
| MEDLINE
| ID: mdl-23232809
ABSTRACT
microRNA abundance has been shown to depend on the amount of the microprocessor components or, in some cases, on specific auxiliary co-factors. In this paper, we show that the FUS/TLS (fused in sarcoma/translocated in liposarcoma) protein, associated with familial forms of Amyotrophic Lateral Sclerosis (ALS), contributes to the biogenesis of a specific subset of microRNAs. Among them, species with roles in neuronal function, differentiation and synaptogenesis were identified. We also show that FUS/TLS is recruited to chromatin at sites of their transcription and binds the corresponding pri-microRNAs. Moreover, FUS/TLS depletion leads to decreased Drosha level at the same chromatin loci. Limited FUS/TLS depletion leads to a reduced microRNA biogenesis and we suggest a possible link between FUS mutations affecting nuclear/cytoplasmic partitioning of the protein and altered neuronal microRNA biogenesis in ALS pathogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
/
Cromatina
/
Proteína FUS de Ligação a RNA
/
MicroRNAs
/
Ribonuclease III
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália