Serine Arginine Splicing Factor 3 Is Involved in Enhanced Splicing of Glucose-6-phosphate Dehydrogenase RNA in Response to Nutrients and Hormones in Liver

Walsh, Callee M.; Suchanek, Amanda L.; Cyphert, Travis J.; Kohan, Alison B.; Szeszel-Fedorowicz, Wioletta; Salati, Lisa M.

doi:10.1074/jbc.m112.410803

Cited by 34 publications

(51 citation statements)

References 49 publications

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“…Under nutrient-rich conditions, insulin induces SRSF3 activity through the phosphorylation of SR proteins. Phosphorylated SRSF3 can then bind G6PD pre-mRNA and promote exon inclusion thus increasing G6PD expression [65, 66]. …”

Section: Rna Processing Directs the Correct Expression Of Key Metamentioning

confidence: 99%

Intersections of post-transcriptional gene regulatory mechanisms with intermediary metabolism

Arif

Datar

Kalsotra

2017

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Intermediary metabolism studies have typically concentrated on four major regulatory mechanisms—substrate availability, allosteric enzyme regulation, post-translational enzyme modification, and regulated enzyme synthesis. Although transcriptional control has been a big focus, it is becoming increasingly evident that many post-transcriptional events are deeply embedded within the core regulatory circuits of enzyme synthesis/breakdown that maintain metabolic homeostasis. The prominent post-transcriptional mechanisms affecting intermediary metabolism include alternative pre-mRNA processing, mRNA stability and translation control, and the more recently discovered regulation by noncoding RNAs. In this review, we discuss the latest advances in our understanding of these diverse mechanisms at the cell-, tissue- and organismal-level. We also highlight the dynamics, complexity and non-linear nature of their regulatory roles in metabolic decision making, and deliberate some of the outstanding questions and challenges in this rapidly expanding field.

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Section: Rna Processing Directs the Correct Expression Of Key Metamentioning

confidence: 99%

Intersections of post-transcriptional gene regulatory mechanisms with intermediary metabolism

Arif

Datar

Kalsotra

2017

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…The decrease in splicing of the nascent transcript is associated with a decrease in the removal of introns surrounding exon 12 of the G6PD mRNA and G6PD pre-mRNA containing these retained introns accumulates prior to its degradation [23]. Exon 12 contains the regulatory elements that are necessary for the nutrient regulation of splicing, which include both an ESS and an ESE [3, 24]. The SR protein, SR splicing factor 3 (SRSF3) binds to the ESE within exon 12, thus increasing splicing of G6PD pre-mRNA during refeeding [24].…”

Section: Introductionmentioning

confidence: 99%

“…Exon 12 contains the regulatory elements that are necessary for the nutrient regulation of splicing, which include both an ESS and an ESE [3, 24]. The SR protein, SR splicing factor 3 (SRSF3) binds to the ESE within exon 12, thus increasing splicing of G6PD pre-mRNA during refeeding [24]. The increase in splicing of G6PD pre-mRNA results in accumulation of mature mRNA and ultimately more G6PD enzyme activity.…”

Section: Introductionmentioning

confidence: 99%

Starvation actively inhibits splicing of glucose-6-phosphate dehydrogenase mRNA via a bifunctional ESE/ESS element bound by hnRNP K

Cyphert

Suchanek

Griffith

et al. 2013

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Regulated expression of glucose-6-phosphate dehydrogenase (G6PD) is due to changes in the rate of pre-mRNA splicing and not changes in its transcription. Starvation alters pre-mRNA splicing by decreasing the rate of intron removal, leading to intron retention and a decrease in the accumulation of mature mRNA. A regulatory element within exon 12 of G6PD pre-mRNA controls splicing efficiency. Starvation caused an increase in the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) K protein and this increase coincided with the increase in the binding of hnRNP K to the regulatory element and a decrease in the expression of G6PD mRNA. HnRNP K bound to two C-rich motifs forming an ESS within exon 12. Overexpression of hnRNP K decreased the splicing and expression of G6PD mRNA, while siRNA-mediated depletion of hnRNP K caused an increase in the splicing and expression of G6PD mRNA. Binding of hnRNP K to the regulatory element was enhanced in vivo by starvation coinciding with a decrease in G6PD mRNA. HnRNP K binding to the C-rich motifs blocked binding of serine-arginine rich, splicing factor 3 (SRSF3), a splicing enhancer. Thus hnRNP K is a nutrient regulated splicing factor responsible for the inhibition of the splicing of G6PD during starvation.

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“…Particularly, arachidonic acid blocks insulin pathway by inhibition of PI3K, while activates kinase p38 [71]. Further, this polyunsaturated fatty acid was shown to decrease phosphorylation of serinearginine-rich proteins, specifically SRSF3, which regulate pre-mRNA splicing by binding to exonic splicing enchancer sites [75]. At the same time, insulin increased phosphorylation of SRSF3 and resulted in correct splicing of G6PDH mRNA.…”

Section: Superoxide Dismutasementioning

confidence: 99%

“…Human gene coding for G6PDH consists of 13 exons. In case of incorrect splicing due to inhibition of SRSF3 binding, introns flanking the exon 12 are retained [75]. This posttranscriptional regulation comprises also splicing silencers, particularly, heterogeneous nuclear ribonucleoproteins (hnRNPs) K, L and A2/B1 which bind to the regulatory sites in G6PDH pre-mRNA near exon 12 in the starved state and dissociate during refeeding [17].…”

Section: Superoxide Dismutasementioning

confidence: 99%

Underinvestigated Roles of Glucose-6-Phosphate Dehydrogenase

Gospodaryov

2015

jpnu

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Serine Arginine Splicing Factor 3 Is Involved in Enhanced Splicing of Glucose-6-phosphate Dehydrogenase RNA in Response to Nutrients and Hormones in Liver

Cited by 34 publications

References 49 publications

Intersections of post-transcriptional gene regulatory mechanisms with intermediary metabolism

Intersections of post-transcriptional gene regulatory mechanisms with intermediary metabolism

Starvation actively inhibits splicing of glucose-6-phosphate dehydrogenase mRNA via a bifunctional ESE/ESS element bound by hnRNP K

Underinvestigated Roles of Glucose-6-Phosphate Dehydrogenase

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