Reading-frame restoration by transcriptional slippage at long stretches of adenine residues in mammalian cells.
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.
Linton
M F
MF
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Raabe
M
M
Pierotti
V
V
Young
S G
SG
D000225:Adenine; D000483:Alleles; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D016366:Open Reading Frames / Q000235:genetics; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
D001055:Apolipoproteins B; D000225:Adenine