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

doi:10.1016/j.cell.2010.09.001

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

Research output: Contribution to journal › Article › peer-review

1403 Scopus citations

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. PaperClip:

Original language	English (US)
Pages (from-to)	46-58
Number of pages	13
Journal	Cell
Volume	143
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2010.09.001
State	Published - Oct 2010
Externally published	Yes

Keywords

DNA
RNA

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2010.09.001

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Long noncoding RNAs with enhancer-like function in human cells. / Ørom, Ulf Andersson; Derrien, Thomas; Beringer, Malte; Gumireddy, Kiranmai; Gardini, Alessandro; Bussotti, Giovanni; Lai, Fan; Zytnicki, Matthias; Notredame, Cedric; Huang, Qihong; Guigo, Roderic; Shiekhattar, Ramin.

In: Cell, Vol. 143, No. 1, 10.2010, p. 46-58.

Research output: Contribution to journal › Article › peer-review

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title = "Long noncoding RNAs with enhancer-like function in human cells",

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. PaperClip:",

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note = "Funding Information: Thanks to the HAVANA team for use of their genome annotation. We also thank the CRG Genomic Facility and the Functional Genomics Core Facility at Wistar and UPenn for expertise in microarray analysis. We thank Dr. Ken Zaret for helpful discussions. U.A.O. is supported by a grant from the Danish Research Council; M.B. is supported by an HFSPO fellowship; A.G. was supported by a fellowship from the American Italian Cancer Foundation; R.G. was supported through Spanish ministry, GENCODE U54 HG004555-01, and NIH; and R.S. was supported by a grant from NIH, GM 079091. ",

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AU - Gardini, Alessandro

AU - Bussotti, Giovanni

AU - Lai, Fan

AU - Zytnicki, Matthias

AU - Notredame, Cedric

AU - Huang, Qihong

AU - Guigo, Roderic

AU - Shiekhattar, Ramin

N1 - Funding Information: Thanks to the HAVANA team for use of their genome annotation. We also thank the CRG Genomic Facility and the Functional Genomics Core Facility at Wistar and UPenn for expertise in microarray analysis. We thank Dr. Ken Zaret for helpful discussions. U.A.O. is supported by a grant from the Danish Research Council; M.B. is supported by an HFSPO fellowship; A.G. was supported by a fellowship from the American Italian Cancer Foundation; R.G. was supported through Spanish ministry, GENCODE U54 HG004555-01, and NIH; and R.S. was supported by a grant from NIH, GM 079091.

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N2 - 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. PaperClip:

AB - 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. PaperClip:

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Long noncoding RNAs with enhancer-like function in human cells

Abstract

Keywords

ASJC Scopus subject areas

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