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.
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: heeyounbunch@gmail.com.
authors.forename: Heeyoun
authors.initials: H
authors.lastname: Bunch
authors.affiliation: Center for Cancer Computational Biology, Dana Farber Cancer Institute, Boston, MA 02130, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Lawney
authors.affiliation: Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27705, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Burkholder
authors.affiliation: BioMicro Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Duanduan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27705, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: BioMicro Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Shmulik
authors.initials: S
authors.lastname: Motola
authors.affiliation: Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27705, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Fargo
authors.affiliation: BioMicro Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Levine
authors.affiliation: Center for Cancer Computational Biology, Dana Farber Cancer Institute, Boston, MA 02130, USA.
authors.forename: Yaoyu E
authors.initials: YE
authors.lastname: Wang
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27705, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Hu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D023281:Genomics / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D008322:Mammals / Q000235:genetics; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; C101116:TRIM28 protein, human; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28; D012319:RNA Polymerase II
keywords: Long non-coding RNAs; RNA polymerase II promoter-proximal pausing; TRIM28