Reading-frame restoration by transcriptional slippage at long stretches of adenine residues in mammalian cells.

Linton MF, Raabe M, Pierotti V, Young SG
J Biol Chem. 1997 272 (22): 14127-32

PMID: 9162040 · DOI:10.1074/jbc.272.22.14127

We previously characterized a mutant apoB allele (the apoB86 allele) that produces both a truncated apoB (apoB86) and a full-length apoB100. The mutant allele contained a deletion of a single cytosine in exon 26, creating a stretch of eight consecutive adenines in the -1 reading frame. The altered reading-frame allele was restored, with approximately 10% efficiency, by the transcriptional insertion of an extra adenine into the stretch of eight consecutive adenines, thereby accounting for the synthesis of the full-length apoB100. Here, we demonstrate that this reading-frame restoration does not occur when the long stretch of adenines is interrupted by a cytosine. To assess whether reading-frame restoration is unique to a single site in the apoB gene, the same mutation (eight consecutive adenines in the -1 reading frame) was inserted into another site within the apoB gene. Reading-frame restoration occurred at the second site and was abrogated when the stretch of adenines was interrupted by another base. Of note, a computerized analysis of human cDNA sequences revealed that long stretches of adenines in protein-coding sequences occur at a lower than predicted frequency, suggesting that evolution has selected against these sequences.

MeSH Terms (9)

Adenine Alleles Animals Apolipoproteins B Evolution, Molecular Humans Open Reading Frames Sequence Analysis, DNA Transcription, Genetic

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