Translation of the FMR1 mRNA is not influenced by AGG interruptions

Anna L. Ludwig, Christopher Raske, Flora Tassone, Dolores Garcia-Arocena, John W. Hershey, Paul J Hagerman

Research output: Contribution to journalArticle

21 Scopus citations

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 ∼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 (<∼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.

Original languageEnglish (US)
Article numbergkp713
Pages (from-to)6896-6904
Number of pages9
JournalNucleic Acids Research
Volume37
Issue number20
DOIs
StatePublished - Sep 14 2009

ASJC Scopus subject areas

  • Genetics

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