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

• Published in: The Journal of biological chemistry Vol. 281; no. 11; pp. 7082 - 7088
• Main Authors: Wills, Norma M., Moore, Barry, Hammer, Andrew, Gesteland, Raymond F., Atkins, John F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-03-2006; American Society for Biochemistry and Molecular Biology
• Subjects: Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Base Sequence; Binding Sites; Cell Line, Tumor; Cloning, Molecular; Computational Biology; Frameshift Mutation; Gene Products, gag - genetics; Glutathione Transferase - metabolism; Humans; Luciferases - metabolism; Molecular Sequence Data; Mutation; Nucleic Acid Conformation; Open Reading Frames; Phylogeny; Retroviridae - genetics; Retroviridae - metabolism; RNA, Messenger - metabolism; Sequence Analysis, Protein
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M511629200

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.