Translation of the FMR1 mRNA is not influenced by AGG interruptions.
Nucleic Acids Res
; 37(20): 6896-904, 2009 Nov.
Article
in En
| MEDLINE
| ID: mdl-19752155
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Biosynthesis
/
Fragile X Mental Retardation Protein
Language:
En
Journal:
Nucleic Acids Res
Year:
2009
Document type:
Article
Affiliation country:
United States