An expanded CAG repeat in Huntingtin Causes +1 frameshifting
Atkins, John F.
American Society for Biochemistry and Molecular Biology
Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the −1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5′ end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1.
Aggregation , Huntington disease , Translation , Translation regulation , Trinucleotide repeat disease , Frameshifting , Seeding
Saffert, P., Adamla, F., Schieweck, R., Atkins, J. F. and Ignatova, Z. (2016) 'An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting', Journal of Biological Chemistry, 291(35), pp. 18505-18513. doi: 10.1074/jbc.M116.744326
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc. This research was originally published in the Journal of Biological Chemistry. Saffert, P., Adamla, F., Schieweck, R., Atkins, J. F. and Ignatova, Z. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting J. Biol. Chem. 2016; 291:pp 18505-18513 © the American Society for Biochemistry and Molecular Biology