RNA polymerase II promoter-proximal pausing in mammalian long non-coding genes

Heeyoun Bunch; Brian P. Lawney; Adam Burkholder; Duanduan Ma; Xiaofeng Zheng; Shmulik Motola; David C. Fargo; Stuart S. Levine; Yaoyu E. Wang; Guang Hu

doi:10.1016/j.ygeno.2016.07.003

RNA polymerase II promoter-proximal pausing in mammalian long non-coding genes

Heeyoun Bunch, Brian P. Lawney, Adam Burkholder, Duanduan Ma, Xiaofeng Zheng, Shmulik Motola, David C. Fargo, Stuart S. Levine, Yaoyu E. Wang, Guang Hu

School of Applied Bioscience

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

39 Scopus citations

Abstract

Mammalian genomes encode a large number of non-coding RNAs (ncRNAs) that greatly exceed mRNA genes. While the physiological and pathological roles of ncRNAs have been increasingly understood, the mechanisms of regulation of ncRNA expression are less clear. Here, our genomic study has shown that a significant number of long non-coding RNAs (lncRNAs, > 1000 nucleotides) harbor RNA polymerase II (Pol II) engaged with the transcriptional start site. A pausing and transcriptional elongation factor for protein-coding genes, tripartite motif-containing 28 (TRIM28) regulates the transcription of a subset of lncRNAs in mammalian cells. In addition, the majority of lncRNAs in human and murine cells regulated by Pol II promoter-proximal pausing appear to function in stimulus-inducible biological pathways. Our findings suggest an important role of Pol II pausing for the transcription of mammalian lncRNA genes.

Original language	English
Pages (from-to)	64-77
Number of pages	14
Journal	Genomics
Volume	108
Issue number	2
DOIs	https://doi.org/10.1016/j.ygeno.2016.07.003
State	Published - 1 Aug 2016

Keywords

Long non-coding RNAs
RNA polymerase II promoter-proximal pausing
TRIM28

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title = "RNA polymerase II promoter-proximal pausing in mammalian long non-coding genes",

abstract = "Mammalian genomes encode a large number of non-coding RNAs (ncRNAs) that greatly exceed mRNA genes. While the physiological and pathological roles of ncRNAs have been increasingly understood, the mechanisms of regulation of ncRNA expression are less clear. Here, our genomic study has shown that a significant number of long non-coding RNAs (lncRNAs, > 1000 nucleotides) harbor RNA polymerase II (Pol II) engaged with the transcriptional start site. A pausing and transcriptional elongation factor for protein-coding genes, tripartite motif-containing 28 (TRIM28) regulates the transcription of a subset of lncRNAs in mammalian cells. In addition, the majority of lncRNAs in human and murine cells regulated by Pol II promoter-proximal pausing appear to function in stimulus-inducible biological pathways. Our findings suggest an important role of Pol II pausing for the transcription of mammalian lncRNA genes.",

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doi = "10.1016/j.ygeno.2016.07.003",

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AU - Bunch, Heeyoun

AU - Lawney, Brian P.

AU - Burkholder, Adam

AU - Ma, Duanduan

AU - Zheng, Xiaofeng

AU - Motola, Shmulik

AU - Fargo, David C.

AU - Levine, Stuart S.

AU - Wang, Yaoyu E.

AU - Hu, Guang

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Mammalian genomes encode a large number of non-coding RNAs (ncRNAs) that greatly exceed mRNA genes. While the physiological and pathological roles of ncRNAs have been increasingly understood, the mechanisms of regulation of ncRNA expression are less clear. Here, our genomic study has shown that a significant number of long non-coding RNAs (lncRNAs, > 1000 nucleotides) harbor RNA polymerase II (Pol II) engaged with the transcriptional start site. A pausing and transcriptional elongation factor for protein-coding genes, tripartite motif-containing 28 (TRIM28) regulates the transcription of a subset of lncRNAs in mammalian cells. In addition, the majority of lncRNAs in human and murine cells regulated by Pol II promoter-proximal pausing appear to function in stimulus-inducible biological pathways. Our findings suggest an important role of Pol II pausing for the transcription of mammalian lncRNA genes.

AB - Mammalian genomes encode a large number of non-coding RNAs (ncRNAs) that greatly exceed mRNA genes. While the physiological and pathological roles of ncRNAs have been increasingly understood, the mechanisms of regulation of ncRNA expression are less clear. Here, our genomic study has shown that a significant number of long non-coding RNAs (lncRNAs, > 1000 nucleotides) harbor RNA polymerase II (Pol II) engaged with the transcriptional start site. A pausing and transcriptional elongation factor for protein-coding genes, tripartite motif-containing 28 (TRIM28) regulates the transcription of a subset of lncRNAs in mammalian cells. In addition, the majority of lncRNAs in human and murine cells regulated by Pol II promoter-proximal pausing appear to function in stimulus-inducible biological pathways. Our findings suggest an important role of Pol II pausing for the transcription of mammalian lncRNA genes.

KW - Long non-coding RNAs

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KW - TRIM28

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RNA polymerase II promoter-proximal pausing in mammalian long non-coding genes

Abstract

Keywords

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