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

The Journal of Biological Chemistry
M F LintonS G Young

Abstract

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.

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Citations

Dec 12, 2012·The Journal of Biological Chemistry·Jeffrey StrathernMikhail Kashlev
Jun 7, 2008·Microbiology and Molecular Biology Reviews : MMBR·Charles L Turnbough, Robert L Switzer
Mar 7, 2006·PLoS Genetics·Martin Ackermann, Lin Chao
Jul 5, 2013·PLoS Genetics·Alasdair J E GordonChristophe Herman
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·B LarsenR F Gesteland
Jul 15, 2004·Proceedings of the National Academy of Sciences of the United States of America·Qi MengRobert L Switzer
Feb 22, 2011·Current Opinion in Microbiology·Charles L Turnbough
Jan 7, 2009·Journal of Neuroscience Research·Tommy A NazwarKarl Schilling
Jul 30, 2011·Journal of Neuroscience Research·Yoshihisa SakaiBernd Sokolowski
Feb 1, 2015·Current Opinion in Microbiology·Alasdair J E GordonChristophe Herman
Mar 21, 1998·American Journal of Medical Genetics·M RaabeS G Young
Mar 23, 2020·Histochemistry and Cell Biology·Adriana MañasJialing Xiang
Apr 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Monika EzerskyteKristian Dreij

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