Repeat Associated Non-ATG Translation Initiation: One DNA, Two Transcripts, Seven Reading Frames, Potentially Nine Toxic Entities!
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{"title"=>"Repeat associated non-ATG translation initiation: One DNA, two transcripts, seven reading frames, potentially nine toxic entities!", "type"=>"generic", "authors"=>[{"first_name"=>"Christopher E.", "last_name"=>"Pearson", "scopus_author_id"=>"7202162472"}], "year"=>2011, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"21423665", "issn"=>"15537390", "sgr"=>"79953745706", "pui"=>"361565230", "scopus"=>"2-s2.0-79953745706", "isbn"=>"1553-7404 (Electronic)\\n1553-7390 (Linking)", "doi"=>"10.1371/journal.pgen.1002018"}, "id"=>"0d82bb71-2180-3964-9c55-54ddd59cb8d3", "abstract"=>"Diseases associated with unstable repetitive elements in the DNA, RNA, and amino acids have consistently revealed scientific surprises. Most diseases are caused by expansions of trinucleotide repeats, which ultimately lead to diseases like Huntington's disease, myotonic dystrophy, fragile X syndrome, and a series of spinocerebellar ataxias. These repeat mutations are dynamic, changing through generations and within an individual, and the repeats can be bi-directionally transcribed. Unsuspected modes of pathogenesis involve aberrant loss of protein expression; aberrant over-expression of non-mutant proteins; toxic-gain-of-protein function through expanded polyglutamine tracts that are encoded by expanded CAG tracts; and RNA-toxic-gain-of-function caused by transcripts harboring expanded CUG, CAG, or CGG tracts. A recent advance reveals that RNA transcripts with expanded CAG repeats can be translated in the complete absence of a starting ATG, and this Repeat Associated Non-ATG translation (RAN-translation) occurs across expanded CAG repeats in all reading frames (CAG, AGC, and GCA) to produce homopolymeric proteins of long polyglutamine, polyserine, and polyalanine tracts. Expanded CTG tracts expressing CUG transcripts also show RAN-translation occurring in all three frames (CUG, UGC, and GCU), to produce polyleucine, polycysteine, and polyalanine. These RAN-translation products can be toxic. Thus, one unstable (CAG)•(CTG) DNA can produce two expanded repeat transcripts and homopolymeric proteins with reading frames (the AUG-directed polyGln and six RAN-translation proteins), yielding a total of potentially nine toxic entities. The occurrence of RAN-translation in patient tissues expands our horizons of modes of disease pathogenesis. Moreover, since RAN-translation counters the canonical requirements of translation initiation, many new questions are now posed that must be addressed. This review covers RAN-translation and some of the pertinent questions.", "link"=>"http://www.mendeley.com/research/repeat-associated-nonatg-translation-initiation-one-dna-two-transcripts-seven-reading-frames-potenti", "reader_count"=>162, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>9, "Researcher"=>40, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>48, "Student > Postgraduate"=>3, "Student > Master"=>18, "Other"=>3, "Student > Bachelor"=>15, "Lecturer"=>3, "Professor"=>11}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>9, "Researcher"=>40, "Student > Doctoral Student"=>9, "Student > Ph. D. Student"=>48, "Student > Postgraduate"=>3, "Student > Master"=>18, "Other"=>3, "Student > Bachelor"=>15, "Lecturer"=>3, "Professor"=>11}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>24, "Mathematics"=>3, "Agricultural and Biological Sciences"=>97, "Medicine and Dentistry"=>18, "Neuroscience"=>5, "Physics and Astronomy"=>1, "Chemistry"=>4, "Psychology"=>1, "Social Sciences"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>18}, "Neuroscience"=>{"Neuroscience"=>5}, "Chemistry"=>{"Chemistry"=>4}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>97}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>24}, "Mathematics"=>{"Mathematics"=>3}, "Unspecified"=>{"Unspecified"=>5}}, "reader_count_by_country"=>{"Czech Republic"=>1, "Turkey"=>3, "United States"=>10, "United Kingdom"=>4, "Italy"=>1, "South Africa"=>1, "France"=>1, "Germany"=>2, "Spain"=>1}, "group_count"=>4}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/791700"], "description"=>"<p>One DNA, two transcripts, seven possible reading frames, potentially nine toxic entities! Both CAG and CTG transcripts could be toxic <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002018#pgen.1002018-Batra1\" target=\"_blank\">[12]</a>, <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002018#pgen.1002018-Li1\" target=\"_blank\">[38]</a>, the AUG-initiated polyGln protein reading frame can be toxic, and each of the three reading frames from either the CAG or CUG transcript present six additional homopolymeric proteins, making a total of nine potentially toxic entities!</p>", "links"=>[], "tags"=>[], "article_id"=>462082, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Christopher E. Pearson"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002018.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RUNning_a_RAN_gene_/462082", "title"=>"RUNning a RAN-gene.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 19:56:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/791759"], "description"=>"<p>Disease-associated repeat sequence can include microsatellites (1–4 bp unit), minisatellites (6–64 bp unit), and megasatellites (several kb unit). GOF, gain-of-function; LOF, loss of function; RNA, toxic RNA. XXas or XXos = XX antisense or XX opposite strand. RAN, repeat associated non-ATG translation.</p><p>Information for the columns: Disorder, Gene, and Locus derived from Online Mendelian Inheritance in Man, OMIM (<a href=\"http://www.ncbi.nlm.nih.gov/omim/\" target=\"_blank\">http://www.ncbi.nlm.nih.gov/omim/</a>); McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD); and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD). Repeat, Repeat size, Pathogenesis and Bi-directional transcription from López Castel et al. <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002018#pgen.1002018-LpezCastel1\" target=\"_blank\">[1]</a>.</p>", "links"=>[], "tags"=>["repeats", "rna"], "article_id"=>462140, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Christopher E. Pearson"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002018.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Unstable_repeats_in_DNA_RNA_proteins_and_human_disease_/462140", "title"=>"Unstable repeats in DNA, RNA proteins, and human disease.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 19:56:43"}

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Relative Metric

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