Long noncoding RNAs with enhancer-like function in human cells.
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.
Ørom
Ulf Andersson
UA
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Derrien
Thomas
T
Beringer
Malte
M
Gumireddy
Kiranmai
K
Gardini
Alessandro
A
Bussotti
Giovanni
G
Lai
Fan
F
Zytnicki
Matthias
M
Notredame
Cedric
C
Huang
Qihong
Q
Guigo
Roderic
R
Shiekhattar
Ramin
R
D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D015894:Genome, Human; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation
D012333:RNA, Messenger; D022661:RNA, Untranslated; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors