An expanded CAG repeat in Huntingtin Causes +1 frameshifting

Simple item page
dc.contributor.authorSaffert, Paul
dc.contributor.authorAdamla, Frauke
dc.contributor.authorSchieweck, Rico
dc.contributor.authorAtkins, John F.
dc.contributor.authorIgnatova, Zoya
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderDeutsche Forschungsgemeinschaften
dc.date.accessioned2018-03-28T14:33:15Z
dc.date.available2018-03-28T14:33:15Z
dc.date.issued2016-07-05
dc.date.updated2018-03-28T14:23:38Z
dc.description.abstractMaintenance 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.en
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (Grants FOR 1805 and SFB 740 )en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSaffert, 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.M116.744326en
dc.identifier.doi10.1074/jbc.M116.744326
dc.identifier.endpage18513en
dc.identifier.issn1083-351X
dc.identifier.issued35en
dc.identifier.journaltitleJournal of Biological Chemistryen
dc.identifier.startpage18505en
dc.identifier.urihttps://hdl.handle.net/10468/5713
dc.identifier.volume291en
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.relation.urihttp://www.jbc.org/content/291/35/18505.abstract
dc.rights© 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 Biologyen
dc.subjectAggregationen
dc.subjectHuntington diseaseen
dc.subjectTranslationen
dc.subjectTranslation regulationen
dc.subjectTrinucleotide repeat diseaseen
dc.subjectFrameshiftingen
dc.subjectSeedingen
dc.titleAn expanded CAG repeat in Huntingtin Causes +1 frameshiftingen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
5109.pdf
Size:
1.72 MB
Format:
Adobe Portable Document Format
Description:
Published version
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Biochemistry and Cell Biology - Journal Articles