An internal ribosome entry site mediates the initiation of soluble guanylyl cyclase β2 mRNA translation

Roberto I. Vazquez-Padron, Si M. Pham, Dania Mateu, Sheik Khan, Abdelouahab Aitouche

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The soluble guanylyl cyclases (sGC), the receptor for nitric oxide, are hete-rodimers 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.

Original languageEnglish (US)
Pages (from-to)3598-3607
Number of pages10
JournalFEBS Journal
Volume275
Issue number14
DOIs
StatePublished - Jul 1 2008

Keywords

  • IRES
  • Nitric oxide
  • Soluble guanylyl cyclase
  • Translation
  • Untranslated region

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'An internal ribosome entry site mediates the initiation of soluble guanylyl cyclase β2 mRNA translation'. Together they form a unique fingerprint.

  • Cite this