Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome 00185, Italy.
Int J Mol Sci. 2013 Jul 11;14(7):14346-73. doi: 10.3390/ijms140714346.
The most part of our genome encodes for RNA transcripts are never translated into proteins. These include families of RNA molecules with a regulatory function, which can be arbitrarily subdivided in short (less than 200 nucleotides) and long non-coding RNAs (ncRNAs). MicroRNAs, which act post-transcriptionally to repress the function of target mRNAs, belong to the first group. Included in the second group are multi-exonic and polyadenylated long ncRNAs (lncRNAs), localized either in the nucleus, where they can associate with chromatin remodeling complexes to regulate transcription, or in the cytoplasm, acting as post-transcriptional regulators. Pluripotent stem cells, such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), represent useful systems for modeling normal development and human diseases, as well as promising tools for regenerative medicine. To fully explore their potential, however, a deep understanding of the molecular basis of stemness is crucial. In recent years, increasing evidence of the importance of regulation by ncRNAs in pluripotent cells is accumulating. In this review, we will discuss recent findings pointing to multiple roles played by regulatory ncRNAs in ESC and iPSCs, where they act in concert with signaling pathways, transcriptional regulatory circuitries and epigenetic factors to modulate the balance between pluripotency and differentiation.
我们基因组中绝大多数编码 RNA 转录本的序列都不会被翻译成蛋白质。这些 RNA 分子家族具有调节功能,可以任意细分为短(小于 200 个核苷酸)和长非编码 RNA(ncRNA)。microRNA 属于第一类,它们在后转录水平抑制靶 mRNA 的功能。第二类包括多外显子和多聚腺苷酸化的长 ncRNA(lncRNA),它们要么定位于细胞核内,与染色质重塑复合物结合以调节转录,要么定位于细胞质内,作为后转录调节因子。多能干细胞,如胚胎干细胞(ESCs)或诱导多能干细胞(iPSCs),是模拟正常发育和人类疾病的有用系统,也是再生医学有前途的工具。然而,为了充分挖掘它们的潜力,深入了解干性的分子基础至关重要。近年来,越来越多的证据表明 ncRNA 在多能细胞中的调控作用非常重要。在这篇综述中,我们将讨论最近的发现,这些发现指出了调控 ncRNA 在 ESC 和 iPSCs 中发挥的多种作用,它们与信号通路、转录调控回路和表观遗传因子协同作用,调节多能性和分化之间的平衡。