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J. Biol. Chem., Vol. 281, Issue 11, 7082-7088, March 17, 2006

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A Functional –1 Ribosomal Frameshift Signal in the Human Paraneoplastic Ma3 Gene^*

Norma M. Wills, Barry Moore, Andrew Hammer, Raymond F. Gesteland, and John F. Atkins¹

From the Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112 and the Biosciences Institute, University College Cork, Cork, Ireland

A bioinformatics approach to finding new cases of –1 frameshifting in the expression of human genes revealed a classical retrovirus-like heptanucleotide shift site followed by a potential structural stimulator in the paraneoplastic antigen Ma3 and Ma5 genes. Analysis of the sequence 3' of the shift site demonstrated that an RNA pseudoknot in Ma3 is important for promoting efficient –1 frame-shifting. Ma3 is a member of a family of six genes in humans whose protein products contain homology to retroviral Gag proteins. The –1 frameshift site and pseudoknot structure are conserved in other mammals, but there are some sequence differences. Although the functions of the Ma genes are unknown, the serious neurological effects of ectopic expression in tumor cells indicate their importance in the brain.

Received for publication, October 27, 2005 , and in revised form, January 4, 2006.

Note Added in Proof—A recent study has independently grouped the six human Ma genes in a family (Schüller, M., Jenne, D., and Voltz, R. (2005) J. Neuroimmunol. 169, 172–176).

^* This work was supported by National Institutes of Health Grants GM71853 (to R. F. G.) and GM48152 (to J. F. A.), who was also supported by an award from Science Foundation Ireland. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S2.

¹ To whom correspondence should be addressed: Dept. of Human Genetics, 15 N. 2030 E., Bldg. 533, Rm. 7410, Salt Lake City, UT 84112-5330. Tel.: 801-585-3434; Fax: 801-585-3910; E-mail: john.atkins{at}genetics.utah.edu.

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