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首页> 外文期刊>Ukrainian Biochemical Journal >Non-coding RNAs and epigenome: de novo DNA methylation, allelic exclusion and X-inactivation
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Non-coding RNAs and epigenome: de novo DNA methylation, allelic exclusion and X-inactivation

机译：非编码RNA和表观基因组：从头DNA甲基化，等位基因排斥和X灭活

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Non-coding RNAs are widespread class of cell RNAs. They participate in many important processes in cells – signaling, posttranscriptional silencing, protein biosynthesis, splicing, maintenance of genome stability, telomere lengthening, X-inactivation. Nevertheless, activity of these RNAs is not restricted to posttranscriptional sphere, but cover also processes that change or maintain the epigenetic information. Non-coding RNAs can directly bind to the DNA targets and cause their repression through recruitment of DNA methyltransferases as well as chromatin modifying enzymes. Such events constitute molecular mechanism of the RNA-dependent DNA methylation. It is possible, that the RNA-DNA interaction is universal mechanism triggering DNA methylation de novo . Allelic exclusion can be also based on described mechanism. This phenomenon takes place, when non-coding RNA, which precursor is transcribed from one allele, triggers DNA methylation in all other alleles present in the cell. Note, that miRNA-mediated transcriptional silencing resembles allelic exclusion, because both miRNA gene and genes, which can be targeted by this miRNA, contain elements with the same sequences. It can be assumed that RNA-dependent DNA methylation and allelic exclusion originated with the purpose of counteracting the activity of mobile genetic elements. Probably, thinning and deregulation of the cellular non-coding RNA pattern allows reactivation of silent mobile genetic elements resulting in genome instability that leads to ageing and carcinogenesis. In the course of X-inactivation, DNA methylation and subsequent heterochromatinization of X chromosome can be triggered by direct hybridization of 5′-end of large non-coding RNA Xist with DNA targets in remote regions of the X chromosome.
机译：非编码RNA是广泛的细胞RNA类。它们参与细胞中的许多重要过程-信号传导，转录后沉默，蛋白质生物合成，剪接，基因组稳定性维持，端粒延长，X灭活。尽管如此，这些RNA的活性并不局限于转录后范围，还涵盖了改变或维持表观遗传信息的过程。非编码RNA可以直接与DNA靶结合，并通过募集DNA甲基转移酶和染色质修饰酶来抑制它们。此类事件构成了RNA依赖性DNA甲基化的分子机制。 RNA-DNA相互作用可能是引发DNA甲基化从头开始的普遍机制。等位基因排除也可以基于所描述的机制。当非编码RNA（一种前体从一个等位基因转录）触发细胞中所有其他等位基因的DNA甲基化时，就会发生这种现象。请注意，miRNA介导的转录沉默类似于等位基因排斥，因为miRNA基因和可被该miRNA靶向的基因均包含具有相同序列的元件。可以假定，RNA依赖性DNA甲基化和等位基因排斥的产生是为了抵消移动遗传元件的活性。可能，细胞非编码RNA模式的减薄和失调使沉默的移动遗传元件重新激活，导致基因组不稳定，从而导致衰老和致癌作用。在X灭活过程中，X染色体的DNA甲基化和随后的异染色质化可以通过将大型非编码RNA Xist的5'-末端与X染色体远处的DNA靶直接杂交来触发。

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