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Mol Cell. 2016 Feb 4;61(3):393-404. doi: 10.1016/j.molcel.2015.12.024. Epub 2016 Jan 28.

Regulated Formation of lncRNA-DNA Hybrids Enables Faster Transcriptional Induction and Environmental Adaptation.

Author information

  • 1Department of Biochemistry, Purdue University, BCHM 305, 175 S. University Street, West Lafayette, IN 47907, USA.
  • 2Department of Biological Sciences, 5047 Gullen Mall, Wayne State University, Detroit, MI 48202, USA.
  • 3Department of Biochemistry, Purdue University, BCHM 305, 175 S. University Street, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, Purdue University, Hansen Life Sciences Research Building, Room 141, 201 S. University Street, West Lafayette, IN 47907, USA; Purdue University Libraries, 504 W. State Street, West Lafayette, IN 47907, USA. Electronic address: ppascuzz@purdue.edu.
  • 4Department of Biochemistry, Purdue University, BCHM 305, 175 S. University Street, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, Purdue University, Hansen Life Sciences Research Building, Room 141, 201 S. University Street, West Lafayette, IN 47907, USA. Electronic address: ejtran@purdue.edu.

Abstract

Long non-coding (lnc)RNAs, once thought to merely represent noise from imprecise transcription initiation, have now emerged as major regulatory entities in all eukaryotes. In contrast to the rapidly expanding identification of individual lncRNAs, mechanistic characterization has lagged behind. Here we provide evidence that the GAL lncRNAs in the budding yeast S. cerevisiae promote transcriptional induction in trans by formation of lncRNA-DNA hybrids or R-loops. The evolutionarily conserved RNA helicase Dbp2 regulates formation of these R-loops as genomic deletion or nuclear depletion results in accumulation of these structures across the GAL cluster gene promoters and coding regions. Enhanced transcriptional induction is manifested by lncRNA-dependent displacement of the Cyc8 co-repressor and subsequent gene looping, suggesting that these lncRNAs promote induction by altering chromatin architecture. Moreover, the GAL lncRNAs confer a competitive fitness advantage to yeast cells because expression of these non-coding molecules correlates with faster adaptation in response to an environmental switch.

PMID:
26833086
PMCID:
PMC4744127
[Available on 2017-02-04]
DOI:
10.1016/j.molcel.2015.12.024
[PubMed - indexed for MEDLINE]
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