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- Title
An internal ribosome entry site mediates the initiation of soluble guanylyl cyclase β2 mRNA translation.
- Authors
Vazquez-Padron, Roberto I.; Pham, Si M.; Mateu, Dania; Sheik Khan; Aitouche, Abdelouahab
- Abstract
The soluble guanylyl cyclases (sGC), the receptor for nitric oxide, are heterodimers consisting of an α- and β-subunit. This study aimed to investigate the translational mechanism of the sGC β2-subunit. Two mRNA species for sGC β2 were isolated from human kidney. These transcripts had dissimilar 5′-untranslated regions (5′-UTRs). The most abundant sGC β2 mRNA showed numerous upstream open reading frames (ORFs) and stable secondary structures that inhibited in vivo and in vitro translation . To evaluate whether these 5′-UTRs harbored an internal ribosome entry site (IRES) that allows translation by an alternative mechanism, we inserted these regions between the two luciferase genes of a bicistronic vector. Transfection of those genetic constructs into HeLa cells demonstrated that both sGC β2 leaders had IRES activity in a cell-type dependent manner. Finally, the secondary structural model of the sGC β2 5′-UTR predicts a Y-type pseudoknot that characterizes the IRES of cellular mRNAs. In conclusion, our findings suggest that sGC β2 5′-UTRs have IRES activity that may permit sGC β2 expression under conditions that are not optimal for scanning-dependent translation.
- Subjects
RIBOSOMES; GUANYLATE cyclase; MESSENGER RNA; GENETIC translation; GENETIC regulation
- Publication
FEBS Journal, 2008, Vol 275, Issue 14, p3598
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2008.06505.x