Facile FMR1 mRNA structure regulation by interruptions in CGG repeats.
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.
Napierala
Marek
M
Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences Noskowskiego 12/14 St, 61-704, Poznan, Poland.
Michalowski
Daniel
D
de Mezer
Mateusz
M
Krzyzosiak
Wlodzimierz J
WJ
D020121:5' Untranslated Regions / Q000737:chemistry; D001483:Base Sequence; D051860:Fragile X Messenger Ribonucleoprotein 1; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D019680:Trinucleotide Repeat Expansion
D020121:5' Untranslated Regions; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human