The hnRNP-Htt axis regulates necrotic cell death induced by transcriptional repression through impaired RNA splicing.
Cell Death Dis
; 7: e2207, 2016 Apr 28.
Article
em En
| MEDLINE
| ID: mdl-27124581
ABSTRACT
In this study, we identify signaling network of necrotic cell death induced by transcriptional repression (TRIAD) by α-amanitin (AMA), the selective RNA polymerase II inhibitor, as a model of neurodegenerative cell death. We performed genetic screen of a knockdown (KD) fly library by measuring the ratio of transformation from pupa to larva (PL ratio) under TRIAD, and selected the cell death-promoting genes. Systems biology analysis of the positive genes mapped on protein-protein interaction databases predicted the signaling network of TRIAD and the core pathway including heterogeneous nuclear ribonucleoproteins (hnRNPs) and huntingtin (Htt). RNA sequencing revealed that AMA impaired transcription and RNA splicing of Htt, which is known as an endoplasmic reticulum (ER)-stabilizing molecule. The impairment in RNA splicing and PL ratio was rescued by overexpresion of hnRNP that had been also affected by transcriptional repression. Fly genetics with suppressor or expresser of Htt and hnRNP worsened or ameliorated the decreased PL ratio by AMA, respectively. Collectively, these results suggested involvement of RNA splicing and a regulatory role of the hnRNP-Htt axis in the process of the transcriptional repression-induced necrosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Proteínas de Drosophila
/
Ribonucleoproteínas Nucleares Heterogêneas
/
Proteína Huntingtina
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Japão