Dysregulated RNA polyadenylation contributes to metabolic impairment in non-alcoholic fatty liver disease.
Nucleic Acids Res
; 50(6): 3379-3393, 2022 04 08.
Article
en En
| MEDLINE
| ID: mdl-35293570
ABSTRACT
Pre-mRNA processing is an essential mechanism for the generation of mature mRNA and the regulation of gene expression in eukaryotic cells. While defects in pre-mRNA processing have been implicated in a number of diseases their involvement in metabolic pathologies is still unclear. Here, we show that both alternative splicing and alternative polyadenylation, two major steps in pre-mRNA processing, are significantly altered in non-alcoholic fatty liver disease (NAFLD). Moreover, we find that Serine and Arginine Rich Splicing Factor 10 (SRSF10) binding is enriched adjacent to consensus polyadenylation motifs and its expression is significantly decreased in NAFLD, suggesting a role mediating pre-mRNA dysregulation in this condition. Consistently, inactivation of SRSF10 in mouse and human hepatocytes in vitro, and in mouse liver in vivo, was found to dysregulate polyadenylation of key metabolic genes such as peroxisome proliferator-activated receptor alpha (PPARA) and exacerbate diet-induced metabolic dysfunction. Collectively our work implicates dysregulated pre-mRNA polyadenylation in obesity-induced liver disease and uncovers a novel role for SRSF10 in this process.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Proteínas de Ciclo Celular
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Poliadenilación
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Enfermedad del Hígado Graso no Alcohólico
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Factores de Empalme Serina-Arginina
Límite:
Animals
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Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
Reino Unido