Transcription and nuclear transport of CAG/CTG trinucleotide repeats in yeast.
Trinucleotide repeats are involved in several neurological disorders in humans. DNA sequences containing CAG/CTG repeats are prone to slippage during replication and double-strand break repair. The effects of trinucleotide repeats on transcription and on nuclear export were analyzed in vivo in yeast. Transcription of a CAG/CTG trinucleotide repeat in the 3'-untranslated region of a URA3 reporter gene leads to transcription of messenger RNAs several kilobases longer than the expected size. These long mRNAs form more readily when CAG rather than CTG repeats are transcribed. CAG- or CUG-containing transcripts show a non-homogeneous cellular localization. We propose that long mRNAs result from transcription slippage, and discuss the possible implications for human diseases.
Fabre
Emmanuelle
E
Unité de Génétique Moléculaire des Levures (URA 2171 CNRS and UFR 927 Université Pierre et Marie Curie) Institut Pasteur, 25 rue du Dr Roux, 75724 Paris cedex 15, France. efabre@pasteur.fr
Dujon
Bernard
B
Richard
Guy-Franck
GF
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D001483:Base Sequence; D015152:Blotting, Northern; D005800:Genes, Fungal / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000235:genetics; D012331:RNA, Fungal / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D018911:Trinucleotide Repeats / Q000235:genetics* / Q000502:physiology*
D020413:3' Untranslated Regions; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D009964:Orotidine-5'-Phosphate Decarboxylase