Mirroring the multifaceted role of RNA and its partners in gene expression.
Mirroring the multifaceted role of RNA and its partners in gene expression.
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反映 RNA 及其伙伴在基因表达中的多方面作用。
DOI：
10.1002/1873-3468.13230
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发表时间：
2018
期刊：
影响因子：
3.5
通讯作者：
Zavolan M
中科院分区：
文献类型：
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作者：
Zavolan M
在分子生物学的早期，人们普遍认为RNA的作用是将DNA中存储的遗传信息传递到多肽中。已知参与这些过程的三种主要类型的 RNA：信使 RNA (mRNA)、转移 RNA (tRNA) 和核糖体 RNA (rRNA)。然而，在过去的半个世纪里，我们对 RNA 类别、功能丰度和多样性的了解急剧增加。核糖体本质上是核酶的发现 [1, 2] 尤其使 RNA 在细胞生命中的核心作用成为人们关注的焦点。千禧年之交也是另一个影响深远的认识的时期，即依赖小RNA的基因表达调控的普遍性[3]。在接下来的十年里，RNA 几乎存在于基因表达的所有调控层中，从基因表达级联顶部的表观遗传层 [4, 5] 到最远端的翻译层 [6]。这种快速转变很大程度上是由人类基因组计划之后开发的测序技术实现的。再加上用于分离各种大小和分子特性的RNA（例如[7]）的巧妙方案和注释各种类别小RNA的计算方法[8]，调节RNA的集合已经迅速扩展和多样化。我们现在知道，< 2% 的人类基因组包含蛋白质编码基因，而 80% 的基因被转录为非编码 RNA (ncRNA)，根据其大小分为小非编码 RNA 和长非编码 RNA (lncRNA)。小 ncRNA 包括经过深入研究的 microRNA (miRNA)，它们被发现在各种癌症类型中增加，并表现出促癌活性 [9]。 LncRNA 是长（> 200 个核苷酸）转录物，在功能上有助于控制细胞分化和维持细胞身份。值得注意的是，由于大多数（约 90%）与疾病相关的单核苷酸多态性位于基因调控或基因间区域，因此长基因间 ncRNA (lincRNA) 尤其可能对未来个性化医疗疗法的发展产生关键影响
In the early years of Molecular Biology, the role of RNA was largely considered to be the transmission of the genetic information stored in the DNA into polypeptides. Three major types of RNA engaged in these processes were known: messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA). However, within the last half century our knowledge about RNA classes, abundance and diversity of functions has increased dramatically. The discovery that the ribosome is essentially a ribozyme [1, 2] especially brought the central role of RNA for cellular life into the spotlight. The turn of the millennium was also the time of another far-reaching realization, that of the pervasiveness of small RNA-dependent regulation of gene expression [3]. Within the decade that followed, RNAs were found in essentially all regulatory layers of gene expression, from the epigenetic layer at the top of the gene expression cascade [4, 5] to the most distal translation layer [6]. Much of this rapid transition was enabled by sequencing technologies that were developed in the wake of the human genome project. Coupled with ingenious protocols for isolating RNAs of various sizes and molecular properties (eg [7]) and computational methods to annotate various classes of small RNAs [8], the set of regulatory RNAs has expanded and diversified rapidly. We now know that< 2% of the human genome contains protein-coding genes, whereas 80% is transcribed into noncoding RNAs (ncRNAs), classified based on their size into small and long noncoding RNAs (lncRNAs). Small ncRNAs include the highly investigated microRNAs (miRNAs) that were found to be increased in various cancer types where they exhibit pro-oncogenic activity [9]. LncRNAs are long (> 200 nucleotides) transcripts that functionally contribute to the control of cell differentiation and maintenance of cell identity. Notably, as most (~ 90%) of disease-associated single nucleotide polymorphisms are located in gene regulatory or intergenic regions, long-intergenic ncRNAs (lincRNAs) in particular may have pivotal impact for the development of personalized medicine therapies in the future