Long antisense non-coding RNAs and the epigenetic regulation of gene expression.

Long antisense non-coding RNAs and the epigenetic regulation of gene expression.
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DOI:
10.1515/bmc-2013-0014
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发表时间:
2013-08-01
影响因子:
--
通讯作者:
Morris, Kevin V
Morris, Kevin V
中科院分区:
其他
文献类型:
--
作者:
Vadaie, Nadia;Morris, Kevin V

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2003年人类基因组计划完成后不久,Encode项目启动。该项目旨在确定人类基因组中的功能元件,出乎意料地发现>80%的基因组被转录。Encode项目确定了由非编码RNA(ncRNA)编码的基因组转录区域。由于只有2%的基因组携带基因编码蛋白质,那么难题是,基因组中这些非编码区的功能是什么?这些ncRNA包括短RNA和长RNA。这篇综述的重点将是反义长非编码RNA(lncRNA),因为这些转录本已被观察到在蛋白质编码基因的基因表达中发挥作用。已经发现一些lncRNA在表观遗传水平上调节蛋白质编码基因的转录,由此它们通过将蛋白质复合物募集到基因组中的靶基因座来抑制转录。相反,有一些lncRNA在基因表达中具有积极的作用,但机制鲜为人知,并且一些lncRNA已被证明参与转录后过程。此外,已观察到lncRNA通过充当诱饵在正反馈环中调节其自身的表达。lncRNA的生物学意义现在才变得明显,许多lncRNA被发现在几种人类疾病中发挥重要作用。
Shortly after the completion of the human genome project in 2003, the Encode project was launched. The project was set out to identify the functional elements in the human genome, and unexpectedly it was found that >80% of the genome is transcribed. The Encode project identified those transcribed regions of the genome to be encoded by non-coding RNAs (ncRNAs). With only 2% of the genome carrying gene-encoding proteins, the conundrum was then, what is the function, if any, of these non-coding regions of the genome? These ncRNAs included both short and long RNAs. The focus of this review will be on antisense long non-coding RNAs (lncRNAs), as these transcripts have been observed to play a role in gene expression of protein-coding genes. Some lncRNAs have been found to regulate protein-coding gene transcription at the epigenetic level, whereby they suppress transcription through the recruitment of protein complexes to target loci in the genome. Conversely, there are lncRNAs that have a positive role in gene expression with less known about mechanism, and some lncRNAs have been shown to be involved in post-transcriptional processes. Additionally, lncRNAs have been observed to regulate their own expression in a positive feedback loop by functioning as a decoy. The biological significance of lncRNAs is only just now becoming evident, with many lncRNAs found to play a significant role in several human diseases.