Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia.
Int J Mol Sci. 2022 Mar 10;23(6):3014. doi: 10.3390/ijms23063014.
Small noncoding RNAs of different origins and classes play several roles in the regulation of gene expression. Here, we show that diverged and rearranged fragments of rDNA units are scattered throughout the human genome and that endogenous small noncoding RNAs are processed by the Microprocessor complex from specific regions of ribosomal RNAs shaping hairpins. These small RNAs correspond to particular sites inside the fragments of rDNA that mostly reside in intergenic regions or the introns of about 1500 genes. The targets of these small ribosomal RNAs (srRNAs) are characterized by a set of epigenetic marks, binding sites of Pol II, RAD21, CBP, and P300, DNase I hypersensitive sites, and by enrichment or depletion of active histone marks. In HEK293T cells, genes that are targeted by srRNAs (srRNA target genes) are involved in differentiation and development. srRNA target genes are enriched with more actively transcribed genes. Our data suggest that remnants of rDNA sequences and srRNAs may be involved in the upregulation or downregulation of a specific set of genes in human cells. These results have implications for diverse fields, including epigenetics and gene therapy.
不同来源和类别的小非编码 RNA 在基因表达调控中发挥多种作用。在这里，我们表明，rDNA 单位的分化和重排片段散布在整个人类基因组中，内源性小非编码 RNA 由 Microprocessor 复合物从核糖体 RNA 的特定区域加工而成，形成发夹。这些小 RNA 对应于 rDNA 片段内部的特定位点，这些片段主要位于基因间区域或约 1500 个基因的内含子中。这些小核糖体 RNA（srRNA）的靶标具有一组表观遗传标记、Pol II、RAD21、CBP 和 P300 的结合位点、DNase I 超敏位点以及活性组蛋白标记的富集或耗尽。在 HEK293T 细胞中，srRNA 靶向的基因（srRNA 靶基因）参与分化和发育。srRNA 靶基因富含转录更活跃的基因。我们的数据表明，rDNA 序列和 srRNA 的残余物可能参与了人类细胞中特定基因的上调或下调。这些结果对包括表观遗传学和基因治疗在内的多个领域具有重要意义。
