The RNA-Binding Protein A1CF Regulates Hepatic Fructose and Glycerol Metabolism via Alternative RNA Splicing

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Date
2019-10-08Type
- Journal Article
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Cited 19 times in
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Cited 19 times in
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Abstract
The regulation of hepatic gene expression has been extensively studied at the transcriptional level; however, the control of metabolism through posttranscriptional gene regulation by RNA-binding proteins in physiological and disease states is less understood. Here, we report a major role for the hormone-sensitive RNA-binding protein (RBP) APOBEC1 complementation factor (A1CF) in the generation of hepatocyte-specific and alternatively spliced transcripts. Among these transcripts are isoforms for the dominant and high-affinity fructose-metabolizing ketohexokinase C and glycerol kinase, two key metabolic enzymes that are linked to hepatic gluconeogenesis and found to be markedly reduced upon hepatic ablation of A1cf. Consequently, mice lacking A1CF exhibit improved glucose tolerance and are protected from fructose-induced hyperglycemia, hepatic steatosis, and development of obesity. Our results identify a previously unreported function of A1CF as a regulator of alternative splicing of a subset of genes influencing hepatic glucose production through fructose and glycerol metabolism. Show more
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https://doi.org/10.3929/ethz-b-000370196Publication status
publishedExternal links
Journal / series
Cell ReportsVolume
Pages / Article No.
Publisher
ElsevierSubject
A1CF; hnRNPH1; Gluconeogenesis; Fructose; Glycerol; Ketohexokinase; Fructokinase; Glycerol kinase; Alternative splicing; RNA binding proteinOrganisational unit
00002 - ETH Zürich02030 - Dep. Biologie / Dep. of Biology
03739 - Stoffel, Markus / Stoffel, Markus
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Show all metadata
Citations
Cited 19 times in
Web of Science
Cited 19 times in
Scopus
ETH Bibliography
yes
Altmetrics