Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications
Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications
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DOI：
10.1093/bfgp/elp038
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发表时间：
2009-11-01
期刊：
影响因子：
--
通讯作者：
Mattick, John S.
中科院分区：
文献类型：
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作者：
Dinger, Marcel E.;Amaral, Paulo P.;Mattick, John S.
对真核生物转录组的全基因组分析表明，大多数基因组都是转录的，产生大量非蛋白质编码的RNA(NcRNAs)。这一令人惊讶的观察结果挑战了关于高等生物的遗传编程以及信息在基因组中如何存储和组织的许多假设。此外，基因组学的快速发展几乎没有给生物学家提供机会将这些新发现整合到他们的智力和实验框架中。人们认为，全基因组研究产生的问题往往多于答案，这反过来又导致了困惑和争议，这让这个问题变得更加复杂。在本文中，我们讨论与普遍转录现象相关的常见问题，并考虑可用于评估所产生的ncRNAs的功能(或缺乏)的指标。我们认为，许多证据，包括表达谱、保守签名、染色质修饰模式和对越来越多的个案的检查，都支持非编码转录的广泛功能。我们还讨论了用于分析蛋白质编码基因的信息学和实验方法如何不适用于ncRNA，以及蛋白质编码基因构成基因组主要信息输出的普遍看法如何导致了围绕普遍转录及其潜在意义的许多误解。最后，我们提出了大多数真核基因组具有功能的概念含义，并描述了欣赏这一观点将如何提供相当大的机会来进一步理解发育和复杂疾病的分子基础。
Genome-wide analyses of the eukaryotic transcriptome have revealed that the majority of the genome is transcribed, producing large numbers of non-protein-coding RNAs (ncRNAs). This surprising observation challenges many assumptions about the genetic programming of higher organisms and how information is stored and organized within the genome. Moreover, the rapid advances in genomics have given little opportunity for biologists to integrate these emerging findings into their intellectual and experimental frameworks. This problem has been compounded by the perception that genome-wide studies often generate more questions than answers, which in turn has led to confusion and controversy. In this article, we address common questions associated with the phenomenon of pervasive transcription and consider the indices that can be used to evaluate the function (or lack thereof) of the resulting ncRNAs. We suggest that many lines of evidence, including expression profiles, conservation signatures, chromatin modification patterns and examination of increasing numbers of individual cases, argue in favour of the widespread functionality of non-coding transcription. We also discuss how informatic and experimental approaches used to analyse protein-coding genesmay not be applicable to ncRNAs and how the general perception that protein-coding genes form the main informational output of the genome has resulted in much of the misunderstanding surrounding pervasive transcription and its potential significance. Finally, we present the conceptual implications of the majority of the eukaryotic genome being functional and describe how appreciating this perspective will provide considerable opportunity to further understand the molecular basis of development and complex diseases.