Splicing regulator SLU7 is essential for maintaining liver homeostasis.
In: Journal of Clinical Investigation, Jg. 124 (2014-07-01), Heft 7, S. 2909-2920
academicJournal
Zugriff:
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 4a (Hnf4a), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence. [ABSTRACT FROM AUTHOR]
Titel: |
Splicing regulator SLU7 is essential for maintaining liver homeostasis.
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Autor/in / Beteiligte Person: | Elizalde, Maria ; Urtasun, Raquel ; Azkona, Maria ; Latasa, Maria U. ; Goñi, Saioa ; García-lrigoyen, Oihane ; Uriarte, Iker ; Segura, Victor ; Collantes, María ; Di Scala, Mariana ; Lujambio, Amaia ; Prieto, Jesús ; Ávila, Matías A. ; Berasain, Carmen |
Zeitschrift: | Journal of Clinical Investigation, Jg. 124 (2014-07-01), Heft 7, S. 2909-2920 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 0021-9738 (print) |
DOI: | 10.1172/JCI74382 |
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