Functional expression of angiotensinogen depends on splicing enhancers in exon 2

Cibele C Cardoso (1) , Daniela A Cabrini (2) , Markus May (1) , Claudia S Bhagat (1) , Nelida Eleno (3) , Cécile Cayla (1) , Thomas Walther (4, 5) , Michael Bader (1)

1 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
2 Department of Pharmacology
3 Department of Physiology and Pharmacology
4 Department Experimental Cardiology
5 University of Hull

Angiotensinogen belongs to the family of serpins and is the only precursor of the potent cardiovascular peptide, angiotensin II, the main effector of the renin-angiotensin system. The gene coding for this protein carries an internal exon (exon 2), the length of which (859bp) by far exceeds the mean length of internal exons in vertebrates (<300bp). Here, we show that this essential exon is skipped in about 20% of all transcripts in liver, brain, and kidney of rats and mice. Deletion mutants of exon 2 revealed a 62bp region located at its 5′-end which is important for its inclusion in the mature angiotensinogen mRNA in transfected COS7 cells. Using an artificial minigene, we defined sequences inside this region as exonic splicing enhancers. These data reveal a novel molecular mechanism important for the renin-angiotensin system with implications in the basic understanding and the therapeutically assessment of cardiovascular diseases.

Mots clés: angiotensinogen; exonic splicing enhancer; alternative splicing

Cibele C Cardoso, Daniela A Cabrini, Markus May, Claudia S Bhagat, Nelida Eleno, et al.. Functional expression of angiotensinogen depends on splicing enhancers in exon 2. Molecular and Cellular Endocrinology, 2010, 332 (1-2), pp.228. ⟨10.1016/j.mce.2010.10.016⟩. ⟨hal-00654962⟩