This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 96/11/1161    most recent 01.RES.0000170651.72198.fav1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weber, M. Articles by Searles, C. D. Search for Related Content PubMed PubMed Citation Articles by Weber, M. Articles by Searles, C. D. Related Collections Gene expression Gene regulation Endothelium/vascular type/nitric oxide

(Circulation Research. 2005;96:1161.)
© 2005 American Heart Association, Inc.

Molecular Medicine

Laminar Shear Stress and 3' Polyadenylation of eNOS mRNA

Martina Weber, Curt H. Hagedorn, David G. Harrison, Charles D. Searles

From the Division of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta Veterans Administration Medical Center, Atlanta, Ga.

Correspondence to Charles D. Searles, Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr, WMB 319, Atlanta, GA 30322. E-mail csearle{at}emory.edu

The 3' poly(A) tail is important in messenger RNA stability and translational efficiency. In somatic tissues, 3' polyadenylation of mRNAs has been thought to largely be a constitutively active process. We have reported that laminar shear stress causes a brief increase in endothelial nitric oxide synthase (eNOS) transcription, followed by a prolonged increase in eNOS mRNA stability. We sought to determine whether shear stress and other stimuli affected eNOS 3' polyadenylation in endothelial cells. Under basal (static) conditions, eNOS mRNA possessed short 3' poly(A) tails of <25 nt. In contrast, laminar shear stress increased expression of eNOS transcripts with long poly(A) tails. ENOS transcripts with longer poly(A) tails had prolonged half-lives (6 hours in static cells versus 18 hours in sheared cells). Polysome analysis revealed that eNOS mRNA from sheared cells was shifted into more translationally active polysome fractions compared with eNOS mRNA from static cells. Shear-induced lengthening of the eNOS 3' poly(A) tail was the result of increased nuclear polyadenylation. Furthermore, hydrogen peroxide and HMG Co-A reductase inhibitors, other stimuli known to modulate eNOS expression posttranscriptionally, also induced eNOS 3' poly(A) tail lengthening. These results support the concept that shear stress modulates eNOS mRNA stability and translation via increased 3' polyadenylation. We suggest that mRNA 3' polyadenylation is a posttranscriptional mechanism used by endothelial cells to regulate gene expression.

Key Words: endothelial nitric oxide synthase • mRNA stability • polyadenylation • posttranscriptional regulation • shear stress

This article has been cited by other articles:

				M. H. Laughlin, S. C. Newcomer, and S. B. Bender Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype J Appl Physiol, March 1, 2008; 104(3): 588 - 600. [Abstract] [Full Text] [PDF]

				I. Kosmidou, J. P. Moore, M. Weber, and C. D. Searles Statin Treatment and 3' Polyadenylation of eNOS mRNA Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2642 - 2649. [Abstract] [Full Text] [PDF]

				D. Won, S.-N. Zhu, M. Chen, A.-M. Teichert, J. E. Fish, C. C. Matouk, M. Bonert, M. Ojha, P. A. Marsden, and M. I. Cybulsky Relative Reduction of Endothelial Nitric-Oxide Synthase Expression and Transcription in Atherosclerosis-Prone Regions of the Mouse Aorta and in an in Vitro Model of Disturbed Flow Am. J. Pathol., November 1, 2007; 171(5): 1691 - 1704. [Abstract] [Full Text] [PDF]

				L. Tang, B. Luo, R. P. Patel, Y. Ling, J. Zhang, and M. B. Fallon Modulation of pulmonary endothelial endothelin B receptor expression and signaling: implications for experimental hepatopulmonary syndrome Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1467 - L1472. [Abstract] [Full Text] [PDF]

				J. E. Fish, C. C. Matouk, E. Yeboah, S. C. Bevan, M. Khan, K. Patil, M. Ohh, and P. A. Marsden Hypoxia-inducible Expression of a Natural cis-Antisense Transcript Inhibits Endothelial Nitric-oxide Synthase J. Biol. Chem., May 25, 2007; 282(21): 15652 - 15666. [Abstract] [Full Text] [PDF]

				P. M. Cummins, N. von Offenberg Sweeney, M. T. Killeen, Y. A. Birney, E. M. Redmond, and P. A. Cahill Cyclic strain-mediated matrix metalloproteinase regulation within the vascular endothelium: a force to be reckoned with Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H28 - H42. [Abstract] [Full Text] [PDF]

				C. D. Searles Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression Am J Physiol Cell Physiol, November 1, 2006; 291(5): C803 - C816. [Abstract] [Full Text] [PDF]

				J. V. van Thienen, J. O. Fledderus, R. J. Dekker, J. Rohlena, G. A. van IJzendoorn, N. A. Kootstra, H. Pannekoek, and A. J.G. Horrevoets Shear stress sustains atheroprotective endothelial KLF2 expression more potently than statins through mRNA stabilization Cardiovasc Res, November 1, 2006; 72(2): 231 - 240. [Abstract] [Full Text] [PDF]

				V. Gambillara, C. Chambaz, G. Montorzi, S. Roy, N. Stergiopulos, and P. Silacci Plaque-prone hemodynamics impair endothelial function in pig carotid arteries Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2320 - H2328. [Abstract] [Full Text] [PDF]