Long noncoding RNAs with enhancer-like function in human cells.

While the long non-coding RNAs (ncRNAs) constitute a large portion of the mammalian transcriptome, their biological functions has remained elusive. A few long ncRNAs that have been studied in any detail silence gene expression in processes such as X-inactivation and imprinting. We used a GENCODE annotation of the human genome to characterize over a thousand long ncRNAs that are expressed in multiple cell lines. Unexpectedly, we found an enhancer-like function for a set of these long ncRNAs in human cell lines. Depletion of a number of ncRNAs led to increased expression of their neighboring protein-coding genes, including the master regulator of hematopoiesis, SCL (also called TAL1), Snai1 and Snai2. Using heterologous transcription assays we demonstrated a requirement for the ncRNAs in mediating such enhancement of gene expression. These results reveal an unanticipated role for a class of long ncRNAs in activation of critical regulators of development and differentiation.

虽然长非编码RNA（ncRNAs）在哺乳动物转录组中占很大比例，但它们的生物学功能仍然难以捉摸。一些经过详细研究的长ncRNAs在X染色体失活和印记等过程中使基因表达沉默。我们利用人类基因组的GENCODE注释来描述在多种细胞系中表达的一千多种长ncRNAs的特征。出乎意料的是，我们在人类细胞系中发现了一组这些长ncRNAs具有类似增强子的功能。一些ncRNAs的缺失导致其邻近的蛋白质编码基因表达增加，包括造血作用的主要调节因子SCL（也称为TAL1）、Snai1和Snai2。通过异源转录分析，我们证明了ncRNAs在介导这种基因表达增强中的必要性。这些结果揭示了一类长ncRNAs在激活发育和分化的关键调节因子方面的一种意想不到的作用。