Derivation of a Structural model for the c-myc IRES
Derivation of a Structural model for the c-myc IRES
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DOI：
10.1006/jmbi.2001.4745
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发表时间：
2001-06-29
影响因子：
5.6
通讯作者：
Willis, AE
中科院分区：
文献类型：
--
作者：
Le Quesne, JPC;Stoneley, M;Willis, AE
我们利用c-myc IRES RNA的化学探测信息来约束结构预测程序，得到了c-myc内部核糖体进入片段(IRES)的二级结构模型。我们的数据表明，IRES本质上是模块化的，可以分为两个结构域，由一个长的非结构化区域连接在一起。IRES的全部功能都需要这两个域。结构域1是一个复杂的元件，包含一个GNNRA顶环和一个重叠的双假结基序，该基序在已发表的RNA结构中是拓扑上唯一的。结构域2是两者中较小的一个，包含一个顶端的AUUU环。我们已经定位了核糖体着陆位置，并表明核糖体进入伪结点下游的16个核苷酸区域的情况与在几个病毒IRESS中观察到的情况相似。为了测试结构，IRES的几个关键区域发生了突变，有趣的是，我们已经确定的一些结构元件似乎具有抑制c-myc IRES功能的功能。这对于通过IRES中发生的突变来解除c-myc表达的调控具有深远的意义。(C)2001年学术出版社。
We have derived a secondary structure model for the c-myc internal ribosome entry segment (IRES) by using information from chemical probing of the c-myc IRES RNA to constrain structure prediction programs. Our data suggest that the IRES is modular in nature, and can be divided into two structural domains linked by a long unstructured region. Both domains are required for full IRES function. Domain 1 is a complex element that contains a GNNRA apical loop and an overlapping double pseudoknot motif that is topologically unique amongst published RNA structures. Domain 2, the smaller of the two, contains an apical AUUU loop.We have located the ribosome landing site and have shown that ribosomes enter in a 16 nt region downstream of the pseudoknots in a situation similar to that observed in several viral IRESs. To test the structure, several key regions of the IRES were mutated and, interestingly, it appears that some of the structural elements that we have identified function to repress c-myc IRES function. This has profound implications for de-regulation of c-myc expression by mutations occurring in the IRES. (C) 2001 Academic Press.