TY  - JOUR
A1  - Saffert, Paul
A1  - Adamla, Frauke
A1  - Schieweck, Rico
A1  - Atkins, John F.
A1  - Ignatova, Zoya
T1  - An Expanded CAG Repeat in Huntingtin Causes+1 Frameshifting
JF  - The journal of biological chemistry
N2  - 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.
KW  - aggregation
KW  - Huntington disease
KW  - translation
KW  - translation regulation
KW  - trinucleotide repeat disease
KW  - frameshifting
KW  - seeding
Y1  - 2016
U6  - https://doi.org/10.1074/jbc.M116.744326
SN  - 0021-9258
SN  - 1083-351X
VL  - 291
SP  - 18505
EP  - 18513
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  -