Peer-Reviewed Journal Details
Mandatory Fields
Saffert, P; Adamla, F;Schieweck, R;Atkins, JF; Ignatova, Z
2016
August
The Journal of Biological Chemistry
An Expanded CAG Repeat in Huntingtin Causes+1 Frameshifting
Validated
WOS: 13 ()
Optional Fields
aggregation Huntington disease translation translation regulation trinucleotide repeat disease frameshifting seeding INTRANUCLEAR INCLUSIONS MOLECULAR ARCHITECTURE CONTAINING PROTEINS RAN TRANSLATION DISORDERS DISEASE YEAST TRANSLOCATION TRANSCRIPTS POLYALANINE
291
18505
18513
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.
10.1074/jbc.M116.744326
Grant Details