Lee Jeannie T
Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
Genes Dev. 2009 Aug 15;23(16):1831-42. doi: 10.1101/gad.1811209.
Transcriptome studies are revealing that the eukaryotic genome actively transcribes a diverse repertoire of large noncoding RNAs (ncRNAs), many of which are unannotated and distinct from the small RNAs that have garnered much attention in recent years. Why are they so pervasive, and do they have a function? X-chromosome inactivation (XCI) is a classic epigenetic phenomenon associated with many large ncRNAs. Here, I provide a perspective on how XCI is achieved in mice and suggest how this knowledge can be applied to the rest of the genome. Emerging data indicate that long ncRNAs can function as guides and tethers, and may be the molecules of choice for epigenetic regulation: First, unlike proteins and small RNAs, large ncRNAs remain tethered to the site of transcription, and can therefore uniquely direct allelic regulation. Second, ncRNAs command a much larger sequence space than proteins, and can therefore achieve very precise spatiotemporal control of development. These properties imply that long noncoding transcripts may ultimately rival small RNAs and proteins in their versatility as epigenetic regulators, particularly for locus- and allele-specific control.
转录组研究表明，真核生物基因组能积极转录各种不同的大型非编码RNA（ncRNA），其中许多未被注释，且与近年来备受关注的小RNA不同。它们为何如此普遍，以及是否具有功能？X染色体失活（XCI）是一种与许多大型ncRNA相关的经典表观遗传现象。在此，我阐述了小鼠中XCI是如何实现的，并提出如何将这一知识应用于基因组的其他部分。新出现的数据表明，长链ncRNA可作为引导分子和锚定分子，可能是表观遗传调控的首选分子：首先，与蛋白质和小RNA不同，大型ncRNA仍锚定在转录位点，因此能够独特地指导等位基因调控。其次，ncRNA所占据的序列空间比蛋白质大得多，因此能够实现对发育非常精确的时空控制。这些特性意味着，作为表观遗传调控因子，长链非编码转录本最终在多功能性方面可能与小RNA和蛋白质相媲美，特别是在基因座和等位基因特异性控制方面。
