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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kong, J.
Right arrow Articles by Liebhaber, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kong, J.
Right arrow Articles by Liebhaber, S. A.

Next Article 

Molecular and Cellular Biology, February 2003, p. 1125-1134, Vol. 23, No. 4
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.4.1125-1134.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The KH-Domain Protein {alpha}CP Has a Direct Role in mRNA Stabilization Independent of Its Cognate Binding Site

Jian Kong, Xinjun Ji, and Stephen A. Liebhaber*

Departments of Genetics and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Received 21 August 2002/ Returned for modification 1 October 2002/ Accepted 13 November 2002

Previous studies suggest that high-level stability of a subset of mammalian mRNAs is linked to a C-rich motif in the 3' untranslated region (3'UTR). High-level expression of human {alpha}-globin mRNA (h{alpha}-globin mRNA) in erythroid cells has been specifically attributed to formation of an RNA-protein complex comprised of a 3'UTR C-rich motif and an associated 39-kDa poly(C) binding protein, {alpha}CP. Documentation of this RNA-protein {alpha}-complex has been limited to in vitro binding studies, and its impact has been monitored by alterations in steady-state mRNA. Here we demonstrate that {alpha}CP is stably bound to h{alpha}-globin mRNA in vivo, that {alpha}-complex assembly on the h{alpha}-globin mRNA is restricted to the 3'UTR C-rich motif, and that {alpha}-complex assembly extends the physical half-life of h{alpha}-globin mRNA selectively in erythroid cells. Significantly, these studies also reveal that an artificially tethered {alpha}CP has the same mRNA-stabilizing activity as the native {alpha}-complex. These data demonstrate a unique contribution of the {alpha}-complex to h{alpha}-globin mRNA stability and support a model in which the sole function of the C-rich motif is to selectively tether {alpha}CP to a subset of mRNAs. Once bound, {alpha}CP appears to be fully sufficient to trigger downstream events in the stabilization pathway.

* Corresponding author. Mailing address: Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, Room 428 CRB, 415 Curie Blvd., Philadelphia, PA 19104. Phone: (215) 898-7834. Fax: (215) 573-5157. E-mail: liebhabe{at}mail.med.upenn.edu.

Molecular and Cellular Biology, February 2003, p. 1125-1134, Vol. 23, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.4.1125-1134.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bolognani, F., Contente-Cuomo, T., Perrone-Bizzozero, N. I. (2009). Novel recognition motifs and biological functions of the RNA-binding protein HuD revealed by genome-wide identification of its targets. Nucleic Acids Res 0: gkp863v1-gkp863 [Abstract] [Full Text]  
  • dos Santos, C. O., Dore, L. C., Valentine, E., Shelat, S. G., Hardison, R. C., Ghosh, M., Wang, W., Eisenstein, R. S., Costa, F. F., Weiss, M. J. (2008). An Iron Responsive Element-like Stem-Loop Regulates {alpha}-Hemoglobin-stabilizing Protein mRNA. J. Biol. Chem. 283: 26956-26964 [Abstract] [Full Text]  
  • Silva, A. L., Ribeiro, P., Inacio, A., Liebhaber, S. A., Romao, L. (2008). Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay. RNA 14: 563-576 [Abstract] [Full Text]  
  • Pullmann, R. Jr., Kim, H. H., Abdelmohsen, K., Lal, A., Martindale, J. L., Yang, X., Gorospe, M. (2007). Analysis of Turnover and Translation Regulatory RNA-Binding Protein Expression through Binding to Cognate mRNAs. Mol. Cell. Biol. 27: 6265-6278 [Abstract] [Full Text]  
  • Ji, X., Kong, J., Carstens, R. P., Liebhaber, S. A. (2007). 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. 27: 3290-3302 [Abstract] [Full Text]  
  • Meng, Q., Rayala, S. K., Gururaj, A. E., Talukder, A. H., O'Malley, B. W., Kumar, R. (2007). Signaling-dependent and coordinated regulation of transcription, splicing, and translation resides in a single coregulator, PCBP1. Proc. Natl. Acad. Sci. USA 104: 5866-5871 [Abstract] [Full Text]  
  • He, Z., Russell, J. E. (2007). Dynamic posttranscriptional regulation of {epsilon}-globin gene expression in vivo. Blood 109: 795-801 [Abstract] [Full Text]  
  • Silva, A. L., Pereira, F. J.C., Morgado, A., Kong, J., Martins, R., Faustino, P., Liebhaber, S. A., Romao, L. (2006). The canonical UPF1-dependent nonsense-mediated mRNA decay is inhibited in transcripts carrying a short open reading frame independent of sequence context. RNA 12: 2160-2170 [Abstract] [Full Text]  
  • Kong, J., Sumaroka, M., Eastmond, D. L., Liebhaber, S. A. (2006). Shared Stabilization Functions of Pyrimidine-Rich Determinants in the Erythroid 15-lipoxygenase and {alpha}-globin mRNAs. Mol. Cell. Biol. 26: 5603-5614 [Abstract] [Full Text]  
  • Wang, S., Zhang, J., Theel, S., Barb, J. J., Munson, P. J., Danner, R. L. (2006). Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements. Nucleic Acids Res 34: 3044-3056 [Abstract] [Full Text]  
  • Inacio, A., Silva, A. L., Pinto, J., Ji, X., Morgado, A., Almeida, F., Faustino, P., Lavinha, J., Liebhaber, S. A., Romao, L. (2004). Nonsense Mutations in Close Proximity to the Initiation Codon Fail to Trigger Full Nonsense-mediated mRNA Decay. J. Biol. Chem. 279: 32170-32180 [Abstract] [Full Text]  
  • VANROBAYS, E., GELUGNE, J.-P., CAIZERGUES-FERRER, M., LAFONTAINE, D. L.J. (2004). Dim2p, a KH-domain protein required for small ribosomal subunit synthesis. RNA 10: 645-656 [Abstract] [Full Text]  
  • Lim, M.-H., Kim, J., Kim, Y.-S., Chung, K.-S., Seo, Y.-H., Lee, I., Kim, J., Hong, C. B., Kim, H.-J., Park, C.-M. (2004). A New Arabidopsis Gene, FLK, Encodes an RNA Binding Protein with K Homology Motifs and Regulates Flowering Time via FLOWERING LOCUS C. Plant Cell 16: 731-740 [Abstract] [Full Text]  
  • Chkheidze, A. N., Liebhaber, S. A. (2003). A Novel Set of Nuclear Localization Signals Determine Distributions of the {alpha}CP RNA-Binding Proteins. Mol. Cell. Biol. 23: 8405-8415 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»