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

Genomics. 2016 Aug;108(2):64-77. doi: 10.1016/j.ygeno.2016.07.003. Epub 2016 Jul 16.

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.

Keywords: Long non-coding RNAs; RNA polymerase II promoter-proximal pausing; TRIM28.

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Expression Regulation
  • Genomics / methods
  • HEK293 Cells
  • Humans
  • Mammals / genetics
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic
  • RNA Polymerase II / genetics*
  • RNA Polymerase II / metabolism
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / metabolism*
  • Transcription, Genetic*
  • Tripartite Motif-Containing Protein 28

Substances

  • Nuclear Proteins
  • RNA, Long Noncoding
  • Repressor Proteins
  • TRIM28 protein, human
  • Trim28 protein, mouse
  • Tripartite Motif-Containing Protein 28
  • RNA Polymerase II