HuR binds a cyclic nucleotide-dependent, stabilizing domain in the 3' untranslated region of Na(+)/glucose cotransporter (SGLT1) mRNA.
Differentiation-dependent expression of the Na(+)/glucose cotransporter (SGLT1) is accompanied by a large, cAMP-dependent increase in stability of its mRNA. Stabilization is mediated by protein binding to a critical uridine-rich element (URE) in its 3' untranslated region. In the present study, we demonstrate that HuR, an RNA binding protein of the embryonic lethal abnormal vision family, binds the SGLT1 URE. HuR binding was increased after elevation of intracellular cAMP levels and was dependent on protein phosphorylation. This interaction was prevented by a substitution mutation previously shown to block cAMP-dependent reporter message stabilization. These results implicate HuR as a key mediator of cAMP-dependent SGLT1 mRNA stabilization.
Loflin
P
P
Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, P.O. Box 20708, Houston, TX 77225, USA.
Lever
J E
JE
D020413:3' Untranslated Regions / Q000378:metabolism*; D000818:Animals; D000954:Antigens, Surface; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D010766:Phosphorylation; D011485:Protein Binding; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1; D013552:Swine; D015854:Up-Regulation
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D000242:Cyclic AMP