Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nat Struct Mol Biol. 2013 Aug;20(8):994-1000. doi: 10.1038/nsmb.2619. Epub 2013 Jul 21.
Transcription of eukaryotic genomes is more widespread than was previously anticipated and results in the production of many non-protein-coding RNAs (ncRNAs) whose functional relevance is poorly understood. Here we demonstrate that ncRNAs can counteract the encroachment of heterochromatin into neighboring euchromatin. We have identified a long ncRNA (termed BORDERLINE) that prevents spreading of the HP1 protein Swi6 and histone H3 Lys9 methylation beyond the pericentromeric repeat region of Schizosaccharomyces pombe chromosome 1. BORDERLINE RNAs act in a sequence-independent but locus-dependent manner and are processed by Dicer into short RNAs referred to as brdrRNAs. In contrast to canonical centromeric short interfering RNAs, brdrRNAs are rarely loaded onto Argonaute. Our analyses reveal an unexpected regulatory activity of ncRNAs in demarcating an epigenetically distinct chromosomal domain that could also be operational in other eukaryotes.
真核生物基因组的转录比之前预期的更为广泛,产生了许多非蛋白编码 RNA(ncRNA),但其功能相关性尚不清楚。在这里,我们证明了 ncRNA 可以阻止异染色质侵入邻近的常染色质。我们已经鉴定出一种长 ncRNA(称为 BORDERLINE),可以防止 HP1 蛋白 Swi6 和组蛋白 H3 Lys9 甲基化在 Schizosaccharomyces pombe 染色体 1 的着丝粒重复区域之外扩散。BORDERLINE RNA 以序列非依赖性但基因座依赖性的方式发挥作用,并被 Dicer 加工成称为 brdrRNA 的短 RNA。与典型的着丝粒短干扰 RNA 不同,brdrRNA 很少被 Argonaute 加载。我们的分析揭示了 ncRNA 在划定具有独特表观遗传的染色体结构域方面的意外调控活性,这在其他真核生物中也可能发挥作用。