Repeat Associated Non-ATG Translation Initiation One DNA, Two Transcripts, Seven Reading Frames, Potentially Nine Toxic Entities! 英文参考文献.docVIP

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Repeat Associated Non-ATG Translation Initiation One DNA, Two Transcripts, Seven Reading Frames, Potentially Nine Toxic Entities! 英文参考文献.doc

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Repeat Associated Non-ATG Translation Initiation One DNA, Two Transcripts, Seven Reading Frames, Potentially Nine Toxic Entities! 英文参考文献

Review RepeatAssociatedNon-ATGTranslationInitiation:One DNA,TwoTranscripts,SevenReadingFrames,Potentially NineToxicEntities! ChristopherE.Pearson1,2 * 1ProgramofGeneticsandGenomeBiology,TheHospitalforSickChildren,Toronto,Ontario,Canada,2DepartmentofMolecularGenetics,UniversityofToronto,Toronto, Ontario,Canada including: aberrant loss-of-protein expression [3]; aberrant over- expression of non-mutant proteins [4–6]; toxic-gain-of-protein Abstract: Diseases associated with unstable repetitive elements in the DNA, RNA, and amino acids have consistently revealed scientific surprises. Most diseases arecausedbyexpansionsoftrinucleotiderepeats,which function through expanded polyglutamine tracts that are encoded byexpandedCAGtracts[3];andRNA-toxic-gain-of-functioncaused bytranscriptsharboringexpandedCUGorCGGtracts[7,8].There ultimately lead to diseases like Huntington’s disease, isevenonediseaseknowntobecausedbybothatoxic-polyglutamine myotonic dystrophy, fragile X syndrome, and a series of andatoxic-RNA,withbotharisingfrombidirectionaltranscription spinocerebellar ataxias. These repeat mutations are acrossbothcomplementaryCAGandCTGrepeatstrands(Table1) dynamic, changing through generations and within an individual, and the repeats can be bi-directionally transcribed.Unsuspectedmodesofpathogenesisinvolve [9–12]. Many regions of the genome are transcribed across both strands, including most of the repeats associated with disease loci, aberrant loss of protein expression; aberrant over- expression of non-mutant proteins; toxic-gain-of-protein functionthroughexpandedpolyglutaminetractsthatare encodedbyexpandedCAGtracts;andRNA-toxic-gain-of- functioncausedbytranscriptsharboringexpandedCUG, CAG, or CGG tracts. A recent advance reveals that RNA transcriptswithexpandedCAGrepeatscanbetranslated in the complete absence of a starting ATG, and this Repeat Associated Non-ATG translation (RAN-translation) occursacrossexpandedCAGrepeatsinallreadingframes (CAG,AGC,andGCA)toprod