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 Chkheidze, A. N.
Right arrow Articles by Liebhaber, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chkheidze, A. N.
Right arrow Articles by Liebhaber, S. A.

Next Article 

Molecular and Cellular Biology, December 2003, p. 8405-8415, Vol. 23, No. 23
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.23.8405-8415.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Novel Set of Nuclear Localization Signals Determine Distributions of the {alpha}CP RNA-Binding Proteins

Alexander N. Chkheidze and Stephen A. Liebhaber*

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

Received 10 June 2003/ Returned for modification 22 July 2003/ Accepted 29 August 2003

{alpha}CPs comprise a subfamily of KH-domain-containing RNA-binding proteins with specificity for C-rich pyrimidine tracts. These proteins play pivotal roles in a broad spectrum of posttranscriptional events. The five major {alpha}CP isoforms are encoded by four dispersed loci. Each isoform contains three repeats of the RNA-binding KH domain (KH1, KH2, and KH3) but lacks other identifiable motifs. To explore the complexity of their respective functions, we examined the subcellular localization of each {alpha}CP isoform. Immunofluorescence studies revealed three distinct distributions: {alpha}CP1 and {alpha}CP2 are predominantly nuclear with specific enrichment of {alpha}CP1 in nuclear speckles, {alpha}CP3 and {alpha}CP4 are restricted to the cytoplasm, and {alpha}CP2-KL, an {alpha}CP2 splice variant, is present at significant levels in both the nucleus and the cytoplasm. We mapped nuclear localization signals (NLSs) for {alpha}CP isoforms. {alpha}CP2 contains two functionally independent NLS. Both NLSs appear to be novel and were mapped to a 9-amino-acid segment between KH2 and KH3 (NLS I) and to a 12-amino-acid segment within KH3 (NLS II). NLS I is conserved in {alpha}CP1, whereas NLS II is inactivated by two amino acid substitutions. Neither NLS is present in {alpha}CP3 or {alpha}CP4. Consistent with mapping studies, deletion of NLS I from {alpha}CP1 blocks its nuclear accumulation, whereas NLS I and NLS II must both be inactivated to block nuclear accumulation of {alpha}CP2. These data demonstrate an unexpected complexity in the compartmentalization of {alpha}CP isoforms and identify two novel NLS that play roles in their respective distributions. This complexity of {alpha}CP distribution is likely to contribute to the diverse functions mediated by this group of abundant RNA-binding proteins.

* Corresponding author. Mailing address: Rm. 428, Clinical Research Building, 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, December 2003, p. 8405-8415, Vol. 23, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.23.8405-8415.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fujimura, K., Kano, F., Murata, M. (2008). Identification of PCBP2, a facilitator of IRES-mediated translation, as a novel constituent of stress granules and processing bodies. RNA 14: 425-431 [Abstract] [Full Text]  
  • Choi, H. S., Kim, C. S., Hwang, C. K., Song, K. Y., Law, P.-Y., Wei, L.-N., Loh, H. H. (2007). Novel function of the poly(C)-binding protein {alpha}CP3 as a transcriptional repressor of the mu opioid receptor gene. FASEB J. 21: 3963-3973 [Abstract] [Full Text]  
  • Akker, S. A., Misra, S., Aslam, S., Morgan, E. L., Smith, P. J., Khoo, B., Chew, S. L. (2007). Pre-Spliceosomal Binding of U1 Small Nuclear Ribonucleoprotein (RNP) and Heterogenous Nuclear RNP E1 Is Associated with Suppression of a Growth Hormone Receptor Pseudoexon. Mol. Endocrinol. 21: 2529-2540 [Abstract] [Full Text]  
  • Perera, R., Daijogo, S., Walter, B. L., Nguyen, J. H. C., Semler, B. L. (2007). Cellular Protein Modification by Poliovirus: the Two Faces of Poly(rC)-Binding Protein. J. Virol. 81: 8919-8932 [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]  
  • 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]  
  • Kosturko, L. D., Maggipinto, M. J., Korza, G., Lee, J. W., Carson, J. H., Barbarese, E. (2006). Heterogeneous Nuclear Ribonucleoprotein (hnRNP) E1 Binds to hnRNP A2 and Inhibits Translation of A2 Response Element mRNAs. Mol. Biol. Cell 17: 3521-3533 [Abstract] [Full Text]  
  • Shin, K.-H., Kang, M. K., Kim, R. H., Christensen, R., Park, N.-H. (2006). Heterogeneous Nuclear Ribonucleoprotein G Shows Tumor Suppressive Effect against Oral Squamous Cell Carcinoma Cells.. Clin. Cancer Res. 12: 3222-3228 [Abstract] [Full Text]  
  • Pio, R., Zudaire, I., Pino, I., Castano, Z., Zabalegui, N., Vicent, S., Garcia-Amigot, F., Odero, M. D., Lozano, M. D., Garcia-Foncillas, J., Calasanz, M. J., Montuenga, L. M. (2004). {alpha}CP-4, Encoded by a Putative Tumor Suppressor Gene at 3p21, But Not Its Alternative Splice Variant {alpha}CP-4a, Is Underexpressed in Lung Cancer. Cancer Res. 64: 4171-4179 [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»