EBM Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Waggoner, S. A.
Right arrow Articles by Liebhaber, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Waggoner, S. A.
Right arrow Articles by Liebhaber, S. A.
Experimental Biology and Medicine 228:387-395 (2003)
© 2003 Society for Experimental Biology and Medicine

MINIREVIEWS

Regulation of {alpha}-Globin mRNA Stability

Shelly A. Waggoner and Stephen A. Liebhaber1

Department of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

mRNA stability is a critical determinant of normal red blood cell development and function. The long half-life of globin mRNA is central to the continued synthesis of globin proteins throughout all stages of erythropoiesis, even as the cells undergo programmed transcriptional arrest during terminal differentiation. Studies of a naturally occurring {alpha}-thalassemic mutation that triggers marked destabilization of {alpha}-globin mRNA first led investigators to search for a stability determinant in the 3'-untranslated region (3'UTR). Analysis of this region identified three cytosine-rich (C-rich) segments that contributed to {alpha}-globin mRNA stability when studied in transfected erythroid cells. Subsequently, in vitro studies demonstrated assembly of a sequence-specific ribonucleic-protein (RNP) complex at this site. Mutations in the 3'UTR that blocked formation of this "{alpha}-complex" in vitro resulted in a parallel destabilization of {alpha}-globin mRNA in transfected cells. Members of the {alpha}-globin poly(C)-binding protein ({alpha}CP) subfamily of heteronuclear (hn) RNP K homology (KH) domain RNA-binding proteins have been identified as essential protein components of the {alpha}-complex. In vitro studies suggested that additional proteins may also contribute to {alpha}-complex structure and/or function. Surveys of additional highly stable mRNAs point to a general function for the {alpha}-complex in mRNA stabilization. In vitro and in vivo analyses indicated that the {alpha}-complex stabilizes {alpha}-globin mRNA by two mechanisms: control of 3'-terminal deadenylation and steric protection of an endoribonuclease-sensitive site. Confirmation of these pathways, determination of their relative importance, and generalization of these findings to additional systems await future studies.

Key Words: mRNA stability • {alpha}-globin mRNA • cytosine-rich regions • {alpha}-globin poly(C)-binding proteins • poly(C)-binding proteins • erythroid-enriched endoribonuclease




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
B. J. Hamilton, X.-W. Wang, J. Collins, D. Bloch, A. Bergeron, B. Henry, B. M. Terry, M. Zan, A. J. Mouland, and W. F. C. Rigby
Separate cis-trans Pathways Post-transcriptionally Regulate Murine CD154 (CD40 Ligand) Expression: A NOVEL FUNCTION FOR CA REPEATS IN THE 3'-UNTRANSLATED REGION
J. Biol. Chem., September 12, 2008; 283(37): 25606 - 25616.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. Mabaera, M. R. Greene, C. A. Richardson, S. J. Conine, C. D. Kozul, and C. H. Lowrey
Neither DNA hypomethylation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin
Blood, January 1, 2008; 111(1): 411 - 420.
[Abstract] [Full Text] [PDF]

Home page
 RNAHome page
Z. Du, J. K. Lee, S. Fenn, R. Tjhen, R. M. Stroud, and T. L. James
X-ray crystallographic and NMR studies of protein-protein and protein-nucleic acid interactions involving the KH domains from human poly(C)-binding protein-2
RNA, July 1, 2007; 13(7): 1043 - 1051.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
X. Ji, J. Kong, R. P. Carstens, and S. A. Liebhaber
The 3' Untranslated Region Complex Involved in Stabilization of Human {alpha}-globin mRNA Assembles in the Nucleus and Serves an Independent Role as a Splice Enhancer
Mol. Cell. Biol., May 1, 2007; 27(9): 3290 - 3302.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. Kong, M. Sumaroka, D. L. Eastmond, and S. A. Liebhaber
Shared Stabilization Functions of Pyrimidine-Rich Determinants in the Erythroid 15-lipoxygenase and {alpha}-globin mRNAs
Mol. Cell. Biol., August 1, 2006; 26(15): 5603 - 5614.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
I. A. Mawji and P. A. Marsden
RNA Transfection Is a Versatile Tool to Investigate Endothelin-1 Posttranscriptional Regulation.
Experimental Biology and Medicine, June 1, 2006; 231(6): 704 - 708.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
G. H. Jacobs, P. A. Stockwell, W. P. Tate, and C. M. Brown
Transterm--extended search facilities and improved integration with other databases
Nucleic Acids Res., January 1, 2006; 34(suppl_1): D37 - D40.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Du, J. K. Lee, R. Tjhen, S. Li, H. Pan, R. M. Stroud, and T. L. James
Crystal Structure of the First KH Domain of Human Poly(C)-binding Protein-2 in Complex with a C-rich Strand of Human Telomeric DNA at 1.7 A
J. Biol. Chem., November 18, 2005; 280(46): 38823 - 38830.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S.-H. Goh, Y. T. Lee, N. V. Bhanu, M. C. Cam, R. Desper, B. M. Martin, R. Moharram, R. B. Gherman, and J. L. Miller
A newly discovered human {alpha}-globin gene
Blood, August 15, 2005; 106(4): 1466 - 1472.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. Jenkins, M. Bitner-Glindzicz, S. Malcolm, C.-C. A. Hu, J. Allison, P. J.D. Winyard, A. M. Gullett, D. F.M. Thomas, R. A. Belk, S. A. Feather, et al.
De Novo Uroplakin IIIa Heterozygous Mutations Cause Human Renal Adysplasia Leading to Severe Kidney Failure
J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2141 - 2149.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R. Canete-Soler, K. S. Reddy, D. R. Tolan, and J. Zhai
Aldolases A and C Are Ribonucleolytic Components of a Neuronal Complex That Regulates the Stability of the Light-Neurofilament mRNA
J. Neurosci., April 27, 2005; 25(17): 4353 - 4364.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. K. Wickenheisser, V. L. Nelson-DeGrave, and J. M. McAllister
Dysregulation of Cytochrome P450 17{alpha}-Hydroxylase Messenger Ribonucleic Acid Stability in Theca Cells Isolated from Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1720 - 1727.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. W. Poustie, J. Carran, K. McEleney, S. J. Dixon, T. P. Anastassiades, and S. M. Bernier
N-Butyryl Glucosamine Increases Matrix Gene Expression by Chondrocytes
J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 610 - 616.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the Society for Experimental Biology and Medicine.