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

J. Biol. Chem., Vol. 280, Issue 45, 37957-37964, November 11, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/45/37957    most recent M502883200v1 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 Jeyaraj, S. Articles by Lee, B. S. Search for Related Content PubMed PubMed Citation Articles by Jeyaraj, S. Articles by Lee, B. S. Social Bookmarking                      What's this?

HuR Stabilizes Vacuolar H⁺-translocating ATPase mRNA during Cellular Energy Depletion^*

From the Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio 43210

V-ATPases are multisubunit membrane proteins that use ATP binding and hydrolysis to transport protons across membranes against a concentration gradient. Although some cell types express plasma membrane forms of these transporters, all eukaryotes require V-ATPases to maintain an acidic pH in membrane-bound compartments of endocytic and secretory networks to facilitate protein trafficking and processing. Mammalian cells that completely lack V-ATPases are not viable; yet, the abundance of V-ATPases can differ among cell types by an order of magnitude or more, requiring precise control of their expression. We previously showed that mRNA stability appears to play a major role in regulating overall abundance of V-ATPases. In this report, we demonstrate that the stability of V-ATPase mRNA is regulated through AU-rich elements in 3'-untranslated regions. Unlike some mRNAs that are short-lived due to the presence of these elements, V-ATPase mRNAs have half-lives of hours to days. However, during stress induced by ATP depletion, AU-rich elements are necessary to maintain stability of these transcripts and their presence in the cytoplasm. HuR, an RNA-binding protein that interacts with and stabilizes AU-rich mRNAs, shows increased binding to some V-ATPase mRNAs during ATP depletion. siRNA-mediated knockdown of HuR results in diminished V-ATPase expression. These results indicate that AU-rich elements and associated proteins can play a role in regulation of even very stable mRNAs by protecting against loss during cellular stress.

Received for publication, March 16, 2005 , and in revised form, September 7, 2005.

^* This work was supported by Grant DK52131 from the National Institutes of Health (to B. S. L.). 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 should be addressed: Dept. of Physiology and Cell Biology, The Ohio State University, 302 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210. Tel.: 614-688-3585; Fax: 614-292-4888; E-mail: lee.2076{at}osu.edu.

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

This article has been cited by other articles:

				S. C. Jeyaraj, D. Dakhlallah, S. R. Hill, and B. S. Lee Expression and distribution of HuR during ATP depletion and recovery in proximal tubule cells Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1255 - F1263. [Abstract] [Full Text] [PDF]