Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
Nat Rev Genet. 2015 Feb;16(2):71-84. doi: 10.1038/nrg3863. Epub 2015 Jan 2.
Diverse classes of RNA, ranging from small to long non-coding RNAs, have emerged as key regulators of gene expression, genome stability and defence against foreign genetic elements. Small RNAs modify chromatin structure and silence transcription by guiding Argonaute-containing complexes to complementary nascent RNA scaffolds and then mediating the recruitment of histone and DNA methyltransferases. In addition, recent advances suggest that chromatin-associated long non-coding RNA scaffolds also recruit chromatin-modifying complexes independently of small RNAs. These co-transcriptional silencing mechanisms form powerful RNA surveillance systems that detect and silence inappropriate transcription events, and provide a memory of these events via self-reinforcing epigenetic loops.
各种类型的 RNA,从小 RNA 到长非编码 RNA,已成为基因表达、基因组稳定性和抵御外来遗传元件的关键调控因子。小 RNA 通过引导包含 Argonaute 的复合物与互补的新生 RNA 支架结合,从而修饰染色质结构并使转录沉默,然后介导组蛋白和 DNA 甲基转移酶的募集。此外,最近的进展表明,染色质相关的长非编码 RNA 支架也可以独立于小 RNA 招募染色质修饰复合物。这些转录相关的沉默机制形成了强大的 RNA 监测系统,可以检测和沉默不合适的转录事件,并通过自我强化的表观遗传环来记忆这些事件。