Jarroux Julien, Morillon Antonin, Pinskaya Marina
ncRNA, epigenetic and genome fluidity, Institut Curie, Centre de Recherche, CNRS UMR 3244, PSL Research University and Université Pierre et Marie Curie, Paris, France.
Adv Exp Med Biol. 2017;1008:1-46. doi: 10.1007/978-981-10-5203-3_1.
The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its central role in cell biology. Since the discovery of DNA at the end of the nineteenth century, RNA has been extensively studied. Many discoveries such as housekeeping RNAs (rRNA, tRNA, etc.) supported the messenger RNA model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding RNAs (ncRNAs) were initially identified in bacteria and then in most eukaryotic organisms. A few long ncRNAs (lncRNAs) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2% encodes proteins, the rest being deemed "non-coding." It was later shown that the genome is pervasively transcribed into many ncRNAs, but their functionality remained controversial. Since then, regulatory lncRNAs have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on lncRNAs, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.In this review, we will discuss the many discoveries that led to the study of lncRNAs, from Friedrich Miescher's "nuclein" in 1869 to the elucidation of the human genome and transcriptome in the early 2000s. We will then focus on the biological relevance during lncRNA evolution and describe their basic features as genes and transcripts. Finally, we will present a non-exhaustive catalogue of lncRNA classes, thus illustrating the vast complexity of eukaryotic transcriptomes.
RNA世界假说认为，生命起源之前的生物是以RNA而非DNA和蛋白质为中心的。尽管现代细胞在40亿年里发生了显著变化，但RNA在细胞生物学中仍保持着核心作用。自19世纪末发现DNA以来，RNA就受到了广泛研究。许多发现，如管家RNA（rRNA、tRNA等），都支持了信使RNA模型，该模型是分子生物学中心法则的支柱，这一法则最初是在20世纪50年代末提出的。30年后，首批调控性非编码RNA（ncRNA）最初在细菌中被鉴定出来，随后在大多数真核生物中也被发现。一些长链非编码RNA（lncRNA），如H19和Xist，在基因组时代之前就已被鉴定，但直到21世纪初它们仍属特例。事实上，当2001年人类基因组序列公布时，研究表明只有约1.2%的序列编码蛋白质，其余的被视为“非编码”序列。后来发现，基因组被广泛转录为许多ncRNA，但其功能仍存在争议。从那时起，调控性lncRNA在许多物种中得到了鉴定，并被证明参与了发育和疾病等过程，揭示了真核细胞中一层新的调控机制。对lncRNA的这一新关注，加上高通量测序技术的出现，伴随着许多新转录本的迅速发现，这些转录本根据特定的转录本特征得到了进一步的鉴定和分类。在这篇综述中，我们将讨论从1869年弗里德里希·米舍尔发现“核素”到21世纪初人类基因组和转录组的阐明这一过程中，促成lncRNA研究的诸多发现。然后，我们将关注lncRNA进化过程中的生物学相关性，并描述它们作为基因和转录本的基本特征。最后，我们将列出一个lncRNA类别的非详尽目录，从而说明真核转录组的巨大复杂性。
