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Nucleic Acids Research, 1994, Vol. 22, No. 1 15-19
© 1994

MOLECULAR BIOLOGY

On the relationship between preferred termination codon contexts and nonsense suppression in human cells

Robin Martin

Krebs Institute for Biomolecular Research, The University of Sheffield PO Box 594, Firth Court, Western Bank, Sheffield S10 2UH, UK

Received November 2, 1993. Accepted November 26, 1993.

The nucleotlde sequences 3' to the translatlonal termination codons in a collection of human genes have been analysed for evidence of a preferred 3' context for natural UAG codons. The aim was to see whether human UAG contexts can be related to the recent demonstration of the effects of 3' context on nonsense suppression in human cells. Since mammalian genomes are known to consist of a patchwork of blocks of sequences or ‘isochores’ with different G + C contents, the collection of genes was split into 5 classes containing genes with similar frequencies of G + C at the 3rd position of synonymous codons. This analysis revealed that the frequency of bases 3' to UAG varies with the G + C frequency of the gene, and that these changes were mirrored by changes in the patterns of bases in GN and AGN strings. The Identity of the next 3' base appears therefore to be determined by genome wide changes In G + C composition, rather than selection to maintain a particular tetranucleotide stop signal. These findings argue strongly that the failure to find bias in the patterns of bases used in human coding sequences is an insensitive guide for the existence of codon usage or codon context effects during translation in human cells.


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