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

J. Biol. Chem., Vol. 277, Issue 4, 2373-2376, January 25, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/4/2373    most recent C100614200v1 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 Ke, Y. Articles by Theil, E. C. Search for Related Content PubMed PubMed Citation Articles by Ke, Y. Articles by Theil, E. C. Social Bookmarking                      What's this?

ACCELERATED PUBLICATION
An mRNA Loop/Bulge in the Ferritin Iron-responsive Element Forms in Vivo and Was Detected by Radical Probing with Cu-1,10-phenantholine and Iron Regulatory Protein Footprinting^*

Yaohuang Ke and Elizabeth C. Theil^§

From Children's Hospital Oakland Research Institute, Oakland, California 94609-1673

Messenger RNA (mRNA) regulatory elements often form helices specifically distorted by loops or bulges, which control protein synthesis rates in vitro. Do such three-dimensional RNA structures form in vivo? We now observe formation of the internal loop/bulge (IL/B structure) in the IRE (iron-responsive element) of ferritin mRNA expressed in HeLa cells, using radical cleavage with Cu-phen (Cu-1,10-phenantholine), and protection of the loop/bulge by the regulatory protein (IRP), expressed by cotransfection. Cu-phen, a metal coordination complex (MC) selected because of binding and cleavage at the IL/B in solution, recognized the same site in mRNA in HeLa cells. Endogenous reductants apparently substituted for the sulfhydryl activation of Cu-phen cleavage in solution. Selective RNA IL/B recognition by Cu-phen in vivo is emphasized by resistance to cleavage of a mutated, IL/B IRE in ferritin mRNA. Development of small MCs even more selective than Cu-phen can exploit three-dimensional mRNA or viral RNA structures in vivo to manipulate RNA function. Formation in vivo of the IL/B in the ferritin IRE, which is associated in vitro with greater repression than single IRE structures in other mRNAs, likely contributes to larger derepression of ferritin synthesis in vivo triggered by signals for the IRE/IRP system.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				W. E. Walden, A. I. Selezneva, J. Dupuy, A. Volbeda, J. C. Fontecilla-Camps, E. C. Theil, and K. Volz Structure of Dual Function Iron Regulatory Protein 1 Complexed with Ferritin IRE-RNA Science, December 22, 2006; 314(5807): 1903 - 1908. [Abstract] [Full Text] [PDF]

				J. D. Tibodeau, P. M. Fox, P. A. Ropp, E. C. Theil, and H. H. Thorp The up-regulation of ferritin expression using a small-molecule ligand to the native mRNA PNAS, January 10, 2006; 103(2): 253 - 257. [Abstract] [Full Text] [PDF]

				J. J. Mayo, P. Kohlhepp, D. Zhang, and J. J. Winzerling Effects of sham air and cigarette smoke on A549 lung cells: implications for iron-mediated oxidative damage Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L866 - L876. [Abstract] [Full Text] [PDF]

				P. C. J. Haasnoot, J. F. Bol, and R. C. L. Olsthoorn A plant virus replication system to assay the formation of RNA pseudotriloop motifs in RNA-protein interactions PNAS, October 28, 2003; 100(22): 12596 - 12600. [Abstract] [Full Text] [PDF]

				E. C. Theil Ferritin: At the Crossroads of Iron and Oxygen Metabolism J. Nutr., May 1, 2003; 133(5): 1549S - 1553. [Abstract] [Full Text] [PDF]

				R. Erlitzki, J. C. Long, and E. C. Theil Multiple, Conserved Iron-responsive Elements in the 3'-Untranslated Region of Transferrin Receptor mRNA Enhance Binding of Iron Regulatory Protein 2 J. Biol. Chem., November 1, 2002; 277(45): 42579 - 42587. [Abstract] [Full Text] [PDF]