Napierala Marek, Michalowski Daniel, de Mezer Mateusz, Krzyzosiak Wlodzimierz J
Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences Noskowskiego 12/14 St, 61-704, Poznan, Poland.
Nucleic Acids Res. 2005 Jan 19;33(2):451-63. doi: 10.1093/nar/gki186. Print 2005.
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.
RNA代谢是与脆性X智力低下（FMR1）基因前突变大小等位基因相关的临床疾病发病机制的主要促成因素。在此，我们确定了众多含有不同数量CGG重复序列和AGG中断的FMR1转录本的结构特性。由含不间断重复序列的转录本形成的发夹稳定性随重复序列长度的增加而增加。即使在重复序列中有单个AGG中断也会显著改变5'UTR片段的折叠，通常会导致分支发夹结构。含有不同长度CGG重复序列但具有共同AGG模式的转录本采用了相似类型的二级结构。我们推测，FMR1 mRNA的中断依赖性结构变体促成了在前突变携带者中观察到的表型多样性。
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