Long non-coding RNAs (lncRNAs) outnumber protein-coding transcripts, but their functions remain largely unknown. In this Review, we discuss the emerging roles of lncRNAs in the control of gene transcription. Some of the best characterized lncRNAs have essential transcription cis-regulatory functions that cannot be easily accomplished by DNA-interacting transcription factors, such as XIST, which controls X-chromosome inactivation, or imprinted lncRNAs that direct allele-specific repression. A growing number of lncRNA transcription units, including CHASERR, PVT1 and HASTER (also known as HNF1A-AS1) act as transcription-stabilizing elements that fine-tune the activity of dosage-sensitive genes that encode transcription factors. Genetic experiments have shown that defects in such transcription stabilizers often cause severe phenotypes. Other lncRNAs, such as lincRNA-p21 (also known as Trp53cor1) and Maenli (Gm29348) contribute to local activation of gene transcription, whereas distinct lncRNAs influence gene transcription in trans. We discuss findings of lncRNAs that elicit a function through either activation of their transcription, transcript elongation and processing or the lncRNA molecule itself. We also discuss emerging evidence of lncRNA involvement in human diseases, and their potential as therapeutic targets.

长非编码 RNA (lncRNA) 的数量超过蛋白质编码转录本，但它们的功能仍然很大程度上未知。在这篇综述中，我们讨论了 lncRNA 在基因转录控制中的新兴作用。一些特征最明确的 lncRNA 具有重要的转录顺式调节功能，而这些功能无法通过 DNA 相互作用的转录因子轻松实现，例如控制 X 染色体失活的XIST或直接等位基因特异性抑制的印记 lncRNA。越来越多的lncRNA转录单位，包括CHASERR 、 PVT1和HASTER （也称为HNF1A-AS1 ）充当转录稳定元件，微调编码转录因子的剂量敏感基因的活性。基因实验表明，此类转录稳定剂的缺陷常常会导致严重的表型。其他 lncRNA，例如lincRNA-p21 （也称为Trp53cor1 ）和Maenli ( Gm29348 ) 有助于基因转录的局部激活，而不同的 lncRNA 则影响反式基因转录。我们讨论了 lncRNA 的发现，这些 lncRNA 通过转录激活、转录物延伸和加工或 lncRNA 分子本身来激发功能。我们还讨论了 lncRNA 参与人类疾病的新证据及其作为治疗靶点的潜力。