repeat associated non-atg translation initiation one dna, two transcripts, seven reading frames, potentially nine toxic entities!重复non-atg相关翻译起始一个dna,两个成绩单、七阅读框架,可能9有毒实体!.pdfVIP

Review Repeat Associated Non-ATG Translation Initiation: One DNA, Two Transcripts, Seven Reading Frames, Potentially Nine Toxic Entities! Christopher E. Pearson1,2* 1 Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, 2 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada including: aberrant loss-of-protein expression [3]; aberrant over- Abstract: Diseases associated with unstable repetitive expression of non-mutant proteins [4–6]; toxic-gain-of-protein elements in the DNA, RNA, and amino acids have function through expanded polyglutamine tracts that are encoded consistently revealed scientific surprises. Most diseases by expanded CAG tracts [3]; and RNA-toxic-gain-of-function caused are caused by expansions of trinucleotide repeats, which by transcripts harboring expanded CUG or CGG tracts [7,8]. There ultimately lead to diseases like Huntington’s disease, is even one disease known to be caused by both a toxic-polyglutamine myotonic dystrophy, fragile X syndrome, and a series of and a toxic-RNA, with both arising from bidirectional transcription spinocerebellar ataxias. These repeat mutations are dynamic, changing through generations and within an across both complementary CAG and CTG repeat strands (Table 1) individual, and the repeats can be bi-directionally [9–12]. Many regions of the genome are transcribed across both transcribed. Unsuspected modes of pathog