Long noncoding RNAs with enhancer-like function in human cells

Orom, Ulf Andersson; Derrien, Thomas; Beringer, Malte; Gumireddy, Kiranmai; Gardini, Alessandro; Bussotti, Giovanni, 1983-; Lai, Fan; Zytnicki, Matthias; Notredame, Cedric; Huang, Qihong; Guigó Serra, Roderic; Shiekhattar, Ramin

doi:http://dx.doi.org/10.1016/j.cell.2010.09.001

Long noncoding RNAs with enhancer-like function in human cells

Citation

Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010; 143(1): 46-58. DOI 10.1016/j.cell.2010.09.001

Abstract

While the long noncoding 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 decreased 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 activation of gene expression. These results reveal an unanticipated role for a class of long ncRNAs in activation of critical regulators of development and differentiation.