Sierzputowska-Gracz H, Theil E C
Department of Biochemistry, North Carolina State University, Raleigh 27695-7622, USA.
Nucleic Acids Symp Ser. 1995(33):203-6.
Noncoding sequences regulate mRNA and DNA function. IREs are a highly conserved family of noncoding mRNA sequences which coordinate ferritin mRNA translation and transferrin receptor mRNA stability by interactions with specific negative regulator protein, the IRP. RNA interactions with the IRP are modulated by cellular iron. The protein IRP binds to the entire IRE causing conformational changes in flanking region [Harrell et al. (1991) PNAS 88:4166-4170). The IRE+FL is the first RNA element encoding both positive and negative translational control and serves as a model mRNA regulatory elements. Folding of the IREs indicated previously by reactivity with chemical and enzymatic probes [E.C Theil (1994) Biochem. J., 304:1-11) is confirmed by using 1H, 15N and 31P (1) NMR) and CD to show that IRE secondary structure [hairpin-hexaloop (HL)/stem/internal loop or bulges] is folded, CD spectra display Mg2+ dependent structural changes in the temperature range used in the studies of IRE function. G/A substitution was shown by NMR and UV-vis to decrease stability of the folded IRE [H.Sierzputowska-Gracz et al. (1995) Nucl. Acids Res. 23:146-153]. A hairpin loop mutation affected only negative translational control.
非编码序列调节mRNA和DNA的功能。IREs是一类高度保守的非编码mRNA序列家族，它们通过与特定的负调节蛋白IRP相互作用来协调铁蛋白mRNA的翻译和转铁蛋白受体mRNA的稳定性。RNA与IRP的相互作用受细胞内铁的调节。蛋白质IRP与整个IRE结合，导致侧翼区域发生构象变化[哈雷尔等人（1991年）《美国国家科学院院刊》88:4166 - 4170]。IRE + FL是第一个编码正、负翻译控制的RNA元件，可作为mRNA调控元件的模型。先前通过与化学和酶探针的反应性表明的IRE折叠[E.C.泰尔（1994年）《生物化学杂志》，304:1 - 11]，通过使用1H、15N和31P（1）核磁共振（NMR）和圆二色性（CD）得以证实，结果表明IRE二级结构[发夹 - 六环（HL）/茎/内环或凸起]已折叠，CD光谱显示在IRE功能研究中所用温度范围内，Mg2 + 依赖性结构变化。核磁共振和紫外可见光谱显示，G/A取代会降低折叠后的IRE的稳定性[H.谢尔兹普托夫斯卡 - 格拉茨等人（1995年）《核酸研究》23:146 - 153]。一个发夹环突变仅影响负向翻译控制。
