生活在RNA世界中

中央教条假设首先将基因复制到信使RNA中,然后将其解码为蛋白质,借助于转移RNA和核糖体RNA。早就知道,RNA的世界不仅仅是这三个类别,但是高通量RNA测序的发展揭示了RNA的活性如何。大部分基因组被转录,没有这些转录本被翻译成蛋白质。由于这些非编码RNA的表征,很明显,其中许多具有调节作用。还揭示了对所有类别的RNA的化学修饰如何影响其行为,例如它们与之相互作用,何时以及在降解之前待了多长时间。

基因组生物学has recently published a special issue onRNA & gene regulation,探索这个新世界。

Perhaps some of the best understood regulatory RNAs are the microRNAs, short RNAs that bind to mRNA which mostly causes downregulation by either degrading the mRNA or preventing it from being translated. Although the mechanisms of miRNA regulation have been very well studied, this has mostly been in isolation. In the special issue,Olivia Rissland and coworkers已经研究了miRNA如何与RNA结合蛋白相互作用以影响mRNA的稳定性,发现miRNA会影响调节RNA稳定性的蛋白质的结合,但并没有像以前认为的那样对Polya尾巴长度产生太大影响。

长的非编码RNA特别是神秘的,可能是因为该术语对于具有多种功能的几类RNA来说是一个术语。Maite Huarte及其同事提供了有用的评论of the different mechanisms of lncRNA function. The special issue also includes a research paper from the same authors, in which they characterized一个特定的lncRNA的作用,品脱。They show PINT acts as tumor suppressor by interacting with the Polycomb Repressor Complex 2, hence regulating the expression of genes involved in tumor invasiveness.

另一类的lncRNA来自反义转录,Wyler等人。已经表明了这一点herpes simplex virus causes widespread antisense transcription在细胞中。这通过预防感染细胞的凋亡来帮助感染,从而使病毒复制和扩散。

除了调节基因表达的非编码RNA,还可以通过更改mRNA本身来实现调控。该问题的两次评论讨论了这些机制。Chuan He及其同事探索了许多不同的化学修饰RNA以及他们的效果,卡尔·沃利(Carl Walkley)和金·比利(Jin Billy Li)讨论了editing of adenosine to inosine在RNA中。

RNA editing is a common theme in the issue, with Walkley and Li and colleagues showing that editing does not seem to be essential in mice, as去除编辑酶是广泛耐受的;Porath et al. showing that, although RNA editing may not be required, it is出现各种各样的动物物种;Yi Xing和同事发现单个人之间的编辑程度,并识别与这些变化相关的序列变体;和Daniel等。识别sequences controlling the efficiency of editing

mRNA的另一个主要变化来源是剪接。尽管有很好的替代示例,这些剪接有助于基因调节,但尚不清楚所有替代剪接是否都是功能性的,或者是否只是剪接的随机变化。特刊中的两篇文章探讨了这一点。约翰·拉斯科(John Rasko)和同事比较了五种不同脊椎动物的剪接,发现在转录本中保留内含子来增加转录组的复杂性。Saudemont et al. look at splicing in single-celled Paramecium and also in humans and conclude that the majority of splice variants are errors and thatthe fitness cost of mis-splicing is a major driver of alternative splicingpatterns.

到目前为止,本期发表的其他三篇文章都研究了RNA结合蛋白如何调节基因。多萝西·斯塔格(Dorothy Staiger)和同事在植物中进行了最早的ICLIP研究之一,以表明GRP7 binds to mRNAs in order to regulate circadian rhythms在拟南芥中。Costello等。研究酵母中的压力如何改变EIF4F与转录本的结合,因此调节翻译。Fowzan Alkuraya及其同事在三个血统家族中的一项研究确定了一个基因的3'UTR中的突变,该突变是影响蛋白质的结合已知会诱导mRNA衰减,从而导致视力受损。

特刊是由访客编辑的Mihaela Zavolanfrom the University of Basel andBrenton Graveleyfrom the University of Connecticut.You can read their editorial discussing these exciting times for RNA researchhere

请注意未来几周将在该问题上发表的未来文章。

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