Dinger Marcel E, Amaral Paulo P, Mercer Timothy R, Mattick John S
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
Brief Funct Genomic Proteomic. 2009 Nov;8(6):407-23. doi: 10.1093/bfgp/elp038. Epub 2009 Sep 21.
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 genes may 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.
对真核生物转录组的全基因组分析表明，基因组的大部分区域都被转录，产生了大量非蛋白质编码RNA（ncRNA）。这一惊人发现挑战了许多关于高等生物基因编程以及信息在基因组中如何存储和组织的假设。此外，基因组学的快速发展几乎没有给生物学家机会将这些新发现整合到他们的知识和实验框架中。而认为全基因组研究往往产生的问题多于答案的这种看法，又加剧了这一问题，进而导致了混乱和争议。在本文中，我们探讨了与广泛转录现象相关的常见问题，并考虑了可用于评估所产生的ncRNA功能（或缺乏功能）的指标。我们认为，包括表达谱、保守特征、染色质修饰模式以及对越来越多单个案例的研究等多方面证据，都支持非编码转录具有广泛的功能。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可能不适用于ncRNA，以及认为蛋白质编码基因构成基因组主要信息输出的普遍观念如何导致了围绕广泛转录及其潜在意义的诸多误解。最后，我们阐述了真核生物基因组大部分区域具有功能的概念含义，并描述了认识到这一观点将如何为进一步理解发育和复杂疾病的分子基础提供大量机会。
