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Molecular and Cellular Biology, October 2003, p. 7055-7067, Vol. 23, No. 19
0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.19.7055-7067.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Identification of mRNAs Associated with
CP2-Containing RNP Complexes
Shelly A. Waggoner and Stephen A. Liebhaber*
Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Received 12 March 2003/
Returned for modification 10 June 2003/
Accepted 1 July 2003
Posttranscriptional controls in higher eukaryotes are central to cell differentiation and developmental programs. These controls reflect sequence-specific interactions of mRNAs with one or more RNA binding proteins. The
-globin poly(C) binding proteins (
CPs) comprise a highly abundant subset of K homology (KH) domain RNA binding proteins and have a characteristic preference for binding single-stranded C-rich motifs.
CPs have been implicated in translation control and stabilization of multiple cellular and viral mRNAs. To explore the full contribution of
CPs to cell function, we have identified a set of mRNAs that associate in vivo with the major
CP2 isoforms. One hundred sixty mRNA species were consistently identified in three independent analyses of
CP2-RNP complexes immunopurified from a human hematopoietic cell line (K562). These mRNAs could be grouped into subsets encoding cytoskeletal components, transcription factors, proto-oncogenes, and cell signaling factors. Two mRNAs were linked to ceroid lipofuscinosis, indicating a potential role for
CP2 in this infantile neurodegenerative disease. Surprisingly,
CP2 mRNA itself was represented in
CP2-RNP complexes, suggesting autoregulatory control of
CP2 expression. In vitro analyses of representative target mRNAs confirmed direct binding of
CP2 within their 3' untranslated regions. These data expand the list of mRNAs that associate with
CP2 in vivo and establish a foundation for modeling its role in coordinating pathways of posttranscriptional gene regulation.
* Corresponding author. Mailing address: Department of Genetics, University of Pennsylvania School of Medicine, Room 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, October 2003, p. 7055-7067, Vol. 23, No. 19
0022-538X/03/$08.00+0 DOI: 10.1128/MCB.23.19.7055-7067.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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