International,  ACL (papers with reading comittee)

Cell, Volume 143, Issue 1, 46-58

01 Oct 2010   Long Noncoding RNAs with Enhancer-like Function in Human Cells

Ulf Andersson Ørom, Thomas Derrien, Malte Beringer, Kiranmai Gumireddy, Alessandro Gardini, Giovanni Bussotti, Fan Lai, Matthias Zytnicki, Cedric Notredame, Qihong Huang, Roderic Guigo, Ramin Shiekhattar

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.