The State of Long Non-Coding RNA Biology.
The State of Long Non-Coding RNA Biology.
复制标题
长期非编码RNA生物学的状态。
DOI：
10.3390/ncrna4030017
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发表时间：
2018-08-10
期刊：
影响因子：
4.3
通讯作者：
Mattick JS
中科院分区：
文献类型：
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作者：
Mattick JS
转录组学研究表明，哺乳动物和其他复杂生物体的绝大多数基因组以高度动态和细胞特异性的模式表达，以产生大量的基因间、反义和内含子长非蛋白编码RNA（lncRNA）。尽管有充分表征的例子，它们与发育复杂性的比例，以及它们与细胞过程，发育和疾病的关联的许多证明，lncRNA仍然被广泛接受为基因调控的主要参与者。这可能反映了对分化和发育的表观遗传控制的程度和精确度的低估，其中lncRNA似乎具有核心作用，可能作为组织和指导分子：大多数lncRNA是核定位的和染色质相关的，其中一些参与形成专门的亚细胞结构域。我建议，重新评估的概念框架的遗传信息和基因表达的4维个体发育的空间组织的多细胞生物体是必要的。连同这一点和对它们的生物学的进一步研究，现在的关键挑战是确定lncRNA的结构-功能关系，这可能有助于其模块化结构的新证据，RNA编辑和修饰在实现表观遗传可塑性中的作用，以及RNA信号传导在经验的跨代遗传中的作用。
Transcriptomic studies have demonstrated that the vast majority of the genomes of mammals and other complex organisms is expressed in highly dynamic and cell-specific patterns to produce large numbers of intergenic, antisense and intronic long non-protein-coding RNAs (lncRNAs). Despite well characterized examples, their scaling with developmental complexity, and many demonstrations of their association with cellular processes, development and diseases, lncRNAs are still to be widely accepted as major players in gene regulation. This may reflect an underappreciation of the extent and precision of the epigenetic control of differentiation and development, where lncRNAs appear to have a central role, likely as organizational and guide molecules: most lncRNAs are nuclear-localized and chromatin-associated, with some involved in the formation of specialized subcellular domains. I suggest that a reassessment of the conceptual framework of genetic information and gene expression in the 4-dimensional ontogeny of spatially organized multicellular organisms is required. Together with this and further studies on their biology, the key challenges now are to determine the structure–function relationships of lncRNAs, which may be aided by emerging evidence of their modular structure, the role of RNA editing and modification in enabling epigenetic plasticity, and the role of RNA signaling in transgenerational inheritance of experience.
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