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Science 5 July 2002:
Vol. 297. no. 5578, pp. 108 - 110
DOI: 10.1126/science.1069757
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Reports

Alternatively Spliced TCR mRNA Induced by Disruption of Reading Frame

Jun Wang, John I. Hamilton, Mark S. Carter,* Shulin Li,dagger Miles F. Wilkinsonddagger

Nonsense codons that prematurely terminate translation generate potentially deleterious truncated proteins. Here, we show that the T cell receptor-beta (TCRbeta ) gene, which acquires in-frame nonsense codons at high frequency during normal lymphocyte development, gives rise to an alternatively spliced transcript [alternative messenger RNA (alt-mRNA)] that skips the offending mutations that generate such nonsense codons. This alt-mRNA is up-regulated by a transfer RNA-dependent scanning mechanism that responds specifically to mutations that disrupt the reading frame. The finding that translation signals regulate the levels of alternatively spliced mRNAs generated in the nucleus may alter the current view of how gene expression is controlled in eukaryotic cells.

Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Box 180, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
*   Present address: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5124, USA.

dagger    Present address: Department of Surgery/Otolaryngology, 2799 West Grand Boulevard, Henry Ford Health System, Detroit, MI 48202, USA.

ddagger    To whom correspondence should be addressed. E-mail: mwilkins{at}mail.mdanderson.org

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