Splicing regulator SLU7 is essential for maintaining liver homeostasis
Fecha de publicación: 
2014
ISSN: 
0021-9738
Cita: 
Elizalde, M.; Urtasun, R. ; Azkona, M.; Latasa, M.; Goñi, S. ; García-Irigoyen, O.; Uriarte, I.; Segura, V. ; Collantes, M. ; Di-Scala, M. ; Lujambio, A. ; Prieto, J.; Ávila, M. ; Berasain, C. (Carmen). Splicing regulator SLU7 is essential for maintaining liver homeostasis. The Journal of Clinical Investigation, 2014, vol. 24, n.7, pp. 2909-2920
Resumen
A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential. Carcinogenesis in the liver develops as the result of hepatocellular de-differentiation and uncontrolled proliferation. Here, we identified SLU7, which encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Additionally, loss of SLU7 also increased hepatocellular proliferation and induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing and/or expression of multiple genes essential for hepatocellular differentiation, including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear factor 4α (Hnf4α), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence.

Ficheros en este registro:
Fichero: 
pdf.pdf
Descripción: 
Tamaño: 
2,88 MB
Formato: 
Adobe PDF


Los ítems de Dadun están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.