Khvorova Anastasia, Reynolds Angela, Jayasena Sumedha D
Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
Cell. 2003 Oct 17;115(2):209-16. doi: 10.1016/s0092-8674(03)00801-8.
Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5'-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Delta0.5 kcal/mol) at the 5'-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC.
微小RNA（miRNA）和小干扰RNA（siRNA）都利用一组共同的细胞蛋白（Dicer和RNA诱导沉默复合体[RISC]）来引发RNA干扰。在接下来的工作中，对已发表的miRNA序列在miRNA前体发夹结构中的内部稳定性进行的统计分析表明，miRNA前体具有更高的灵活性，尤其是在5'-反义（AS）末端碱基对处。在siRNA中也观察到了相同的趋势，功能性双链体在5'-AS末端的内部稳定性（Δ0.5千卡/摩尔）低于非功能性双链体。在引入长RNA序列后从植物细胞中回收的siRNA分子的平均内部稳定性也显示出这种特征性的热力学特征。总之，这些结果表明，siRNA的热力学性质在决定分子的功能和寿命方面起着关键作用，可能会影响双链解旋和RISC链保留所涉及的步骤。
