HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 21, 14685-14693, May 23, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/21/14685    most recent M801933200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, M.-X. Articles by Wang, X. L. Search for Related Content PubMed PubMed Citation Articles by Zhang, M.-X. Articles by Wang, X. L. Social Bookmarking                      What's this?

Biogenesis of Short Intronic Repeat 27-Nucleotide Small RNA from Endothelial Nitric-oxide Synthase Gene^*

Ming-Xiang Zhang¹, Cheng Zhang, Ying H. Shen, Jian Wang, Xiao Nan Li, Yun Zhang, Joseph Coselli, and Xing Li Wang²

From the Adult Section of Cardiothoracic Surgery, Texas Heart Institute at St Luke's Episcopal Hospital, Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030 and The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Qilu Hospital, Jinan, Shandong 250100, China

Endothelial nitric-oxide synthase (eNOS) is a constitutively expressed gene in endothelium that produces NO and is critical for vascular integrity. Previously, we reported that the 27-nucleotide (nt) repeat polymorphism in eNOS intron 4, a source of 27-nt small RNA, which inhibits eNOS expression, were associated with cardiovascular risk and expression of the eNOS gene. In the current study, we investigated the biogenesis of the intron 4-derived 27-nt small RNA. Using Northern blot, we showed that the eNOS-derived 27-nt short intronic repeat RNA (sir-RNA) expressed only in the eNOS expressing endothelial cells. Cells containing 10 x 27- or 5 x 27-nt repeats produced higher levels of 27nt sir-RNA and lower levels of eNOS mRNA than the cells with 4 x 27-nt repeats. The 27nt sir-RNA was mostly present within the endothelial nuclei. When the splicing junctions of the 27-nt repeat containing intron 4 in the full-length eNOS cDNA vector were mutated, 27nt sir-RNA biogenesis was abolished. Suppression of Drosha or Dicer diminished the biogenesis of the 27nt sir-RNA. Our study suggests that the 27nt sir-RNA derived through eNOS pre-mRNA splicing may represent a new class of small RNA. The more eNOS is transcribed or higher number of the 27-nt repeats, the more 27nt sir-RNA is produced, which functions as a negative feedback self-regulator by specifically inhibiting the host gene eNOS expression. This novel molecular model may be responsible for quantitative differences between individuals carrying different numbers of the polymorphic repeats hence the cardiovascular risk.

Received for publication, March 10, 2008 , and in revised form, April 3, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health NHLBI Grants R01HL071608, R01HL066053, and P50HL083794 (to X. L. W.). This work was also supported by American Heart Association Grants 0440001N and 0565134Y (to X. L. W.) and National 973 Research Project Grant 2006CB503803 (to C. Z.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence may be addressed. E-mail: mzhang1{at}bcm.edu.

² To whom correspondence may be addressed: BCM 390, One Baylor Plaza, Houston, TX 77030. Tel.: 832-355-9939; Fax: 832-355-9951; E-mail: xlwang{at}bcm.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M.-X. Zhang, C. Zhang, Y. H. Shen, J. Wang, X.-N. Li, L. Chen, Y. Zhang, J. S. Coselli, and X. L. Wang Effect of 27nt Small RNA on Endothelial Nitric-Oxide Synthase Expression Mol. Biol. Cell, September 1, 2008; 19(9): 3997 - 4005. [Abstract] [Full Text] [PDF]