Differentiating protein-coding and noncoding RNA: challenges and ambiguities.

Differentiating protein-coding and noncoding RNA: challenges and ambiguities.
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DOI:
10.1371/journal.pcbi.1000176
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发表时间:
2008-11
影响因子:
4.3
通讯作者:
Mattick JS
Mattick JS
中科院分区:
生物学2区
文献类型:
--
作者:
Dinger ME;Pang KC;Mercer TR;Mattick JS

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RNA可以很容易地分为蛋白质编码和非蛋白质编码两类,这一假设已经在生物学中普及了近50年。直到最近,这两类之间的区别还相对简单:大多数转录本都清楚地被鉴定为蛋白质编码信使RNAs(MRNAs),并很容易与少数特征良好的非蛋白质编码RNAs(NcRNAs)区分开来,如转运体、核糖体和剪接体RNAs。最近的全基因组研究揭示了数千个非编码转录本的存在,其功能和意义尚不清楚。这种隐藏转录组的发现及其对我们理解遗传信息的表达和调控的隐含挑战,使得区分mRNAs和ncRNAs的必要性变得更加迫切和复杂。在这篇综述中,我们考虑了用来区分蛋白质编码转录本和非编码转录本的不同策略,以及表面上看起来似乎是一个简单问题所固有的根本困难。错误注释也可能是双向的:一些ncRNA实际上可能编码多肽,而目前认为的一些可能不这样做。此外,最近的研究表明,一些RNA既可以作为mRNAs发挥作用,也可以作为功能性的ncRNAs发挥作用,这可能是一个相对普遍的现象。我们的结论是,很难明确地将RNA注释为蛋白质编码或非编码,重叠的蛋白质编码和非编码转录本进一步混淆了这一区别。此外,一些转录本既可以在RNA水平上固有地发挥作用,又可以编码蛋白质,这一发现表明mRNAs和ncRNAs之间存在错误的二分法。因此,任何转录本在RNA水平上的功能都不应被忽视。
The assumption that RNA can be readily classified into either protein-coding or non-protein–coding categories has pervaded biology for close to 50 years. Until recently, discrimination between these two categories was relatively straightforward: most transcripts were clearly identifiable as protein-coding messenger RNAs (mRNAs), and readily distinguished from the small number of well-characterized non-protein–coding RNAs (ncRNAs), such as transfer, ribosomal, and spliceosomal RNAs. Recent genome-wide studies have revealed the existence of thousands of noncoding transcripts, whose function and significance are unclear. The discovery of this hidden transcriptome and the implicit challenge it presents to our understanding of the expression and regulation of genetic information has made the need to distinguish between mRNAs and ncRNAs both more pressing and more complicated. In this Review, we consider the diverse strategies employed to discriminate between protein-coding and noncoding transcripts and the fundamental difficulties that are inherent in what may superficially appear to be a simple problem. Misannotations can also run in both directions: some ncRNAs may actually encode peptides, and some of those currently thought to do so may not. Moreover, recent studies have shown that some RNAs can function both as mRNAs and intrinsically as functional ncRNAs, which may be a relatively widespread phenomenon. We conclude that it is difficult to annotate an RNA unequivocally as protein-coding or noncoding, with overlapping protein-coding and noncoding transcripts further confounding this distinction. In addition, the finding that some transcripts can function both intrinsically at the RNA level and to encode proteins suggests a false dichotomy between mRNAs and ncRNAs. Therefore, the functionality of any transcript at the RNA level should not be discounted.
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