Regulation of Angiotensin Type 1 Receptor Function by an Upstream Short Open Reading Frame (sORF) in the mRNA 5' Leader Sequence

Abstract

The angiotensin type 1 receptor (AT1R) plays a critical role in blood pressure control. In this study, we investigated the role of an upstream short open reading frame (sORF) in AT1aR signaling. We investigated Angiotensin II (Ang II)- and Sar1,Ile4,Ile8-Ang II (SII)-induced extracellular signal regulated kinases 1 and 2 (ERK1/2) signaling and its alteration in the presence of an sORF in exon (E) 2 in the AT1aR mRNA 5’ leader sequence (LS). Human embryonic kidney 293 cells (HEK293) were transfected with WT [E1,2,3-AT1aR-EGFP] or MT [E1,2(-108T),3-AT1aR-EGFP]. A single nucleotide was mutated at the start codon of the intact sORF (WT) to create a disrupted sORF (MT). Dose response curves for ERK1/2 activation in WT vs MT were significantly different for Ang II (p