Facile FMR1 mRNA structure regulation by interruptions in CGG repeats
AUTOR(ES)
Napierala, Marek
FONTE
Oxford University Press
RESUMO
RNA metabolism is a major contributor to the pathogenesis of clinical disorders associated with premutation size alleles of the fragile X mental retardation (FMR1) gene. Herein, we determined the structural properties of numerous FMR1 transcripts harboring different numbers of both CGG repeats and AGG interruptions. The stability of hairpins formed by uninterrupted repeat-containing transcripts increased with the lengthening of the repeat tract. Even a single AGG interruption in the repeated sequence dramatically changed the folding of the 5′UTR fragments, typically resulting in branched hairpin structures. Transcripts containing different lengths of CGG repeats, but sharing a common AGG pattern, adopted similar types of secondary structures. We postulate that interruption-dependent structure variants of the FMR1 mRNA contribute to the phenotype diversity, observed in premutation carriers.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=548340Documentos Relacionados
- The effect of FMR1 CGG repeat interruptions on mutation frequency as measured by sperm typing.
- Familial transmission of the FMR1 CGG repeat
- Cloned human FMR1 trinucleotide repeats exhibit a length- and orientation-dependent instability suggestive of in vivo lagging strand secondary structure.
- Ectopic expression of CGG containing mRNA is neurotoxic in mammals
- Mosaicism for the fragile X syndrome full mutation and deletions within the CGG repeat of the FMR1 gene.