title: Translation of the FMR1 mRNA is not influenced by AGG interruptions.
abstract: The fragile X mental retardation 1 (FMR1) gene contains a CGG-repeat element within its 5' untranslated region (5'UTR) which, for alleles with more than approximately 40 repeats, increasingly affects both transcription (up-regulation) and translation (inhibition) of the repeat-containing RNA with increasing CGG-repeat length. Translational inhibition is thought to be due to impaired ribosomal scanning through the CGG-repeat region, which is postulated to form highly stable secondary/tertiary structure. One striking difference between alleles in the premutation range (55-200 CGG repeats) and those in the normal range (< approximately 40 repeats) is the reduced number/absence of 'expansion stabilizing' AGG interruptions in the larger alleles. Such interruptions, which generally occur every 9-11 repeats in normal alleles, are thought to disrupt the extended CGG-repeat hairpin structure, thus facilitating translational initiation. To test this hypothesis, we have measured the translational efficiency of CGG-repeat mRNAs with 0-2 AGG interruptions, both in vitro (rabbit reticulocyte lysates) and in cell culture (HEK-293 cells). We demonstrate that the AGG interruptions have no detectable influence on translational efficiency in either a cell-free system or cell culture, indicating that any AGG-repeat-induced alterations in secondary/tertiary structure, if present, do not involve the rate-limiting step(s) in translational initiation.
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, 4303 Tupper Hall, Davis, CA 95616, USA.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Ludwig
authors.forename: Christopher
authors.initials: C
authors.lastname: Raske
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: Dolores
authors.initials: D
authors.lastname: Garcia-Arocena
authors.forename: John W
authors.initials: JW
authors.lastname: Hershey
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hagerman
mesh_terms: D001483:Base Sequence; D030561:Databases, Nucleic Acid; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C497683:FMR1 protein, human