Epinephrine-Induced Reduction in Insulin Receptor mRNA Level and Stability in U-937 Human Promonocytic Cells

Abstract

The administration of 1O M epinephrine transiently decreased insulin receptor (lR) mRNA levels in U-937 human promonocytic cells, which reached their minimum value after 24 hours. Such a decrease seems to be due, at least in part, to a reduction in transcript stability, since the IR mRNA half-life was observed to decline from approximately 4 h in untreated cells to 3 h in epinephrine-treated cells. Computer inspection of the sequence of the 3' untranslated region of the human IR mRNA showed nine AUUUA pentamers and three U-rich regions. These domains could be targets for a RNA-binding protein induced by treatment with epinephrine producing a destabilization of IR mRNA in U-937 cells.

Identification of two functional estrogen response elements complexed with AP-1-like sites in the human insulin receptor gene promoter

“…Finally, in the case of the human cyclin D1 gene, there was no classical ERE, and the repression by E 2 via ER␤ involved both a cyclic AMP-response element (CRE) and an AP-1-like site in the promoter of this gene [57]. Therefore, To find which mechanism was involved in the transcriptional repression of the hIR gene by E 2 we performed a computer search for candidate ERE sequences by homology with the consensus vit-ERE, in the −1819 to −271 bp of the hIR gene promoter, using our SEQFIND programme [36]. We found no sequence identical to this consensus ERE in this promoter, and neither was any sequence found to show 9 or 8 of the 10 bases of this consensus.…”

“…Potential ERE sequences in the hIR gene promoter were identified by their homology with this consensus vit-ERE using the SEQFIND programme developed in our laboratory [36]. Identification of other potential cis-elements covering, flanking or overlapping these potential EREs, was performed with both the TRANSFAC system [37] and the SEQFIND programme [36].…”

“…We then made a computer search for candidate EREs sequences in the −1819 to −271 bp of the hIR gene promoter by homology with the vit-ERE consensus, using the SEQFIND programme developed in our laboratory [36]. The first results of our search indicated no sequence identical to this consensus ERE in this promoter, and neither was any sequence found to show 9 or 8 of the 10 bases of this consensus.…”

“…This hIR ERE1 also has 5 of the 7 bases of the 5 half-element and 5 of 7 bases of the 3 half-element of the optimal binding sequence ERE (Table 1). We checked for possible cis-elements related to this ERE using both the TRANSFAC system [37], and our SEQFIND programme [36]. We detected an AP-1-like site (5 of 7 bases) covering the 3 half-element of this ERE, another AP-1-like site (4 of 7 bases) overlapping this last AP-1-like site, and finally a third AP-1-like site (5 of 7 bases) adjacent to the 5 half-element (Table 1).…”

1,25-Dihydroxyvitamin D3 effects on the regulation of the insulin receptor gene in the hind limb muscle and heart of streptozotocin-induced diabetic rats

“…The results in Table 3 reveal the presence of one (AUUUA) pentamer, three (AUUUUA) hexamers, and the presence of various U-rich domains: six with five U (no identified in the table), one with seven U and one with ten U. This high number of destabilizing elements is higher than that detected in the 3'-UTRs of other mRNAs considered as highly regulated mRNAs [22]. We hypothesize that the 9.5 Kb INSR species would possess all these destabilizing elements and be more affected than the 7.5 Kb INSR species.…”