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Molecular and Cellular Biology, September 2001, p. 5879-5888, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5879-5888.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Structural and Functional Analysis of an mRNP Complex That Mediates the High Stability of Human beta -Globin mRNA

Jia Yu1 and J. Eric Russell1,2,*

Departments of Medicine1 (Hematology/Oncology) and Pediatrics (Hematology),2 University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104

Received 12 April 2001/Returned for modification 10 May 2001/Accepted 7 June 2001

Human globins are encoded by mRNAs exhibiting high stabilities in transcriptionally silenced erythrocyte progenitors. Unlike alpha -globin mRNA, whose stability is enhanced by assembly of a specific messenger RNP (mRNP) alpha  complex on its 3' untranslated region (UTR), neither the structure(s) nor the mechanism(s) that effects the high-level stability of human beta -globin mRNA has been identified. The present work describes an mRNP complex assembling on the 3' UTR of the beta -globin mRNA that exhibits many of the properties of the stability-enhancing alpha  complex. The beta -globin mRNP complex is shown to contain one or more factors homologous to alpha CP, a 39-kDa RNA-binding protein that is integral to alpha -complex assembly. Sequence analysis implicates a specific 14-nucleotide pyrimidine-rich track within its 3' UTR as the site of beta -globin mRNP assembly. The importance of this track to mRNA stability is subsequently verified in vivo using mice expressing human beta -globin transgenes that contain informative mutations in this region. In combination, the in vitro and in vivo analyses indicate that the high stabilities of the alpha - and beta -globin mRNAs are maintained through related mRNP complexes that may share a common regulatory pathway.

* Corresponding author. Mailing address: Abramson Research Building, Room 316F, The Children's Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104. Phone: (215) 590-3880. Fax: (215) 590-4834. E-mail: jeruss{at}mail.med.upenn.edu.

Molecular and Cellular Biology, September 2001, p. 5879-5888, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5879-5888.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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