title: Starvation actively inhibits splicing of glucose-6-phosphate dehydrogenase mRNA via a bifunctional ESE/ESS element bound by hnRNP K.
abstract: 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.
authors: Department of Biochemistry, West Virginia University, Morgantown, WV 26506, USA.
authors: T J
authors: TJ
authors: Cyphert
authors: A L
authors: AL
authors: Suchanek
authors: B N
authors: BN
authors: Griffith
authors: L M
authors: LM
authors: Salati
mesh_terms: D000818:Animals; D005091:Exons; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D056945:Hep G2 Cells; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007438:Introns; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D013217:Starvation
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D005954:Glucosephosphate Dehydrogenase
keywords: Liver; Nutrient regulation; SRSF3; hnRNP K; mRNA splicing
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