Long noncoding RNAs as enhancers of gene expression.

The human genome contains thousands of long noncoding RNAs (ncRNAs) transcribed from diverse genomic locations. A large set of long ncRNAs is transcribed independent of protein-coding genes. We have used the GENCODE annotation of the human genome to identify 3019 long ncRNAs expressed in various human cell lines and tissue. This set of long ncRNAs responds to differentiation signals in primary human keratinocytes and is coexpressed with important regulators of keratinocyte development. Depletion of a number of these long ncRNAs leads to the repression of specific genes in their surrounding locus, supportive of an activating function for ncRNAs. Using reporter assays, we confirmed such activating function and show that such transcriptional enhancement is mediated through the long ncRNA transcripts. Our studies show that long ncRNAs exhibit functions similar to classically defined enhancers, through an RNA-dependent mechanism.

人类基因组包含数千种从不同基因组位置转录而来的长链非编码RNA（ncRNAs）。大量长链非编码RNA的转录独立于蛋白质编码基因。我们利用人类基因组的GENCODE注释，鉴定出在多种人类细胞系和组织中表达的3019种长链非编码RNA。这组长链非编码RNA对原代人类角质形成细胞中的分化信号有反应，并与角质形成细胞发育的重要调节因子共同表达。对其中一些长链非编码RNA的去除会导致其周围基因座中特定基因的抑制，这支持了非编码RNA具有激活功能。通过报告基因检测，我们证实了这种激活功能，并表明这种转录增强是通过长链非编码RNA转录本介导的。我们的研究表明，长链非编码RNA通过一种依赖RNA的机制，表现出与经典定义的增强子相似的功能。