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Molecular and Cellular Biology, November 2007, p. 7848-7855, Vol. 27, No. 22
0270-7306/07/$08.00+0     doi:10.1128/MCB.00793-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

SBP2 Binding Affinity Is a Major Determinant in Differential Selenoprotein mRNA Translation and Sensitivity to Nonsense-Mediated Decay{triangledown} ,{dagger}

Jeffrey E. Squires, Ilko Stoytchev, Erin P. Forry,{ddagger} and Marla J. Berry*

Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813

Received 5 May 2007/ Returned for modification 30 May 2007/ Accepted 29 August 2007

Selenoprotein mRNAs are potential targets for degradation via nonsense-mediated decay due to the presence of in-frame UGA codons that can be decoded as either selenocysteine or termination codons. When UGA decoding is inefficient, as occurs when selenium is limiting, termination occurs at these positions. Based on the predicted exon-intron structure, 14 of the 25 human selenoprotein mRNAs are predicted to be sensitive to nonsense-mediated decay. Among these, sensitivity varies widely, resulting in a hierarchy of preservation or degradation of selenoprotein mRNAs and, thus, of selenoprotein synthesis. Potential factors in dictating the hierarchy of selenoprotein synthesis are the Sec insertion sequence RNA-binding proteins, SBP2 and nucleolin. To investigate the mechanistic basis for this hierarchy and the role of these two proteins, we carried out knockdowns of SBP2 expression and assessed the effects on selenoprotein mRNA levels. We also investigated in vivo binding of selenoprotein mRNAs by SBP2 and nucleolin via immunoprecipitation of the proteins and quantitation of bound mRNAs. We report that SBP2 exhibits strong preferential binding to some selenoprotein mRNAs over others, whereas nucleolin exhibits minimal differences in binding. Thus, SBP2 is a major determinant in dictating the hierarchy of selenoprotein synthesis via differential selenoprotein mRNA translation and sensitivity to nonsense-mediated decay.

* Corresponding author. Mailing address: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Suite 222, Honolulu, HI 96813. Phone: (808) 692-1506. Fax: (808) 692-1968. E-mail: mberry{at}hawaii.edu

{triangledown} Published ahead of print on 10 September 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, CA.

Molecular and Cellular Biology, November 2007, p. 7848-7855, Vol. 27, No. 22
0270-7306/07/$08.00+0     doi:10.1128/MCB.00793-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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