题目:2018_Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them
摘要:
RNA分子能折叠成复杂的形状,调控基因表达。这篇综述中,我们谈论,目前真核生物中5'UTR结构的机制理解,以及现有的探测5’UTR结构的方法。这些结构能通过RNA结构中螺旋介导的重塑和高级的RNA互作来调控依赖帽子的翻译起始,以及通过IRES,mRNA modification, other specialized translation pathways来调控不依赖帽子的翻译的起始
简介:
1.ancient RNA world:
main catalytic, self-replicating and information carrying component pre-dating cellular life.
2.RNA structure-directed function(primarily in bacteria and archaea but also in algae,fungi and plants):
2.1 ribozymes
2.2 metabolite-sensing riboswitches
3.the role of RNA structure (ancient eukaryotes):
3.1 splicing
3.2 gene regulation by non-coding RNAs
4. mRNA structure with functions in translation initiation, which is ultimately linked to the ribosome
5. the great number of protein and RNA components :
ribosome initiation, scanning, elongation and recycling of mRNA highlights that translation -especially in translation initiation, which is one of the most crucial steps in translation - is a highly regulated process.
RNA结构重排的因素:ribosome and RNA remodellers such as RNA helicases.
提出的科学问题:
how much regulatory potential is encoded in mRNA structures or in the structure-mediated sensing and recruitment of interacting factors such as RNA-binding proteins or trans-acting RNAs?
6.UTR脱离了蛋白编码的限制,可以形成watson-crick配对,和non watson-crick配对,影响翻译的每一步
7.折叠RNA结构的算法表明,UTR有能力参与复杂的RNA碱基配对,复杂的RNA碱基配对能响应protein binding 而发生变化,还能影响the recruitment of ribiosome
x.3'UTR也能调控翻译,另外,5'UTR中非结构化的,线性的元件也可以调控翻译,比如,uORF,kozak sequence(translation initiation sites).
x.5‘UTR如何block或者recruit ribosomes 以及other regulatory factors进行快速的,动态的响应多种细胞环境来调控基因表达。
预测5’UTR二级结构的两个参数:
1.高GC含量 2.一个较高的负折叠自由能;5'UTR上高GC的区段会导致43S预起始复合物的低效扫描和低效起始,高GC5‘UTR和抑制翻译起始成正相关,二级结构的预测和细胞功能的相关性并没有被很好的建立起,预测出来的最稳定的RNA结构有最低的自由能。虽然鉴定完整RNA结构的自由能需要考虑RNA结构域从完全折叠到完全线性的转变,但是扫描的时候只需要RNA结构的局部融化melting,而不是对整个RNA结构都线性化。事实上,已经有一些证据表明,强的局部的RNA二级结构和蛋白互作能阻止核糖体的扫描。
结论:
5ʹ UTR structures in ribosome scanning
真核生物中mRNA的翻译起始于5'端,有5‘帽子和UTR,UTR是核糖体进入位点,有些mRNA缺少完整的5’UTR,比如哺乳动物线粒体中所有的mRNA,但是这种情况在高等动物中是罕见的。