題目：2018_Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them
摘要:
RNA分子能折疊成復(fù)雜的形狀，調(diào)控基因表達。這篇綜述中，我們談?wù)?，目前真核生物?'UTR結(jié)構(gòu)的機制理解，以及現(xiàn)有的探測5’UTR結(jié)構(gòu)的方法。這些結(jié)構(gòu)能通過RNA結(jié)構(gòu)中螺旋介導(dǎo)的重塑和高級的RNA互作來調(diào)控依賴帽子的翻譯起始，以及通過IRES，mRNA modification, other specialized translation pathways來調(diào)控不依賴帽子的翻譯的起始
簡介：
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結(jié)構(gòu)重排的因素：ribosome and RNA remodellers such as RNA helicases.
提出的科學(xué)問題：
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脫離了蛋白編碼的限制，可以形成watson-crick配對，和non watson-crick配對，影響翻譯的每一步
7.折疊RNA結(jié)構(gòu)的算法表明，UTR有能力參與復(fù)雜的RNA堿基配對，復(fù)雜的RNA堿基配對能響應(yīng)protein binding 而發(fā)生變化，還能影響the recruitment of ribiosome
x.3'UTR也能調(diào)控翻譯，另外，5'UTR中非結(jié)構(gòu)化的，線性的元件也可以調(diào)控翻譯，比如，uORF，kozak sequence(translation initiation sites).
x.5‘UTR如何block或者recruit ribosomes 以及other regulatory factors進行快速的，動態(tài)的響應(yīng)多種細胞環(huán)境來調(diào)控基因表達。
預(yù)測5’UTR二級結(jié)構(gòu)的兩個參數(shù)：
1.高GC含量 2.一個較高的負(fù)折疊自由能；5'UTR上高GC的區(qū)段會導(dǎo)致43S預(yù)起始復(fù)合物的低效掃描和低效起始，高GC5‘UTR和抑制翻譯起始成正相關(guān)，二級結(jié)構(gòu)的預(yù)測和細胞功能的相關(guān)性并沒有被很好的建立起，預(yù)測出來的最穩(wěn)定的RNA結(jié)構(gòu)有最低的自由能。雖然鑒定完整RNA結(jié)構(gòu)的自由能需要考慮RNA結(jié)構(gòu)域從完全折疊到完全線性的轉(zhuǎn)變，但是掃描的時候只需要RNA結(jié)構(gòu)的局部融化melting，而不是對整個RNA結(jié)構(gòu)都線性化。事實上，已經(jīng)有一些證據(jù)表明，強的局部的RNA二級結(jié)構(gòu)和蛋白互作能阻止核糖體的掃描。
結(jié)論：
5? UTR structures in ribosome scanning
真核生物中mRNA的翻譯起始于5'端，有5‘帽子和UTR，UTR是核糖體進入位點，有些mRNA缺少完整的5’UTR,比如哺乳動物線粒體中所有的mRNA，但是這種情況在高等動物中是罕見的。
