title: Regulated Formation of lncRNA-DNA Hybrids Enables Faster Transcriptional Induction and Environmental Adaptation.
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.
authors.affiliation: Department of Biochemistry, Purdue University, BCHM 305, 175 S. University Street, West Lafayette, IN 47907, USA.
authors.forename: Sara C
authors.initials: SC
authors.lastname: Cloutier
authors.affiliation: Department of Biochemistry, Purdue University, BCHM 305, 175 S. University Street, West Lafayette, IN 47907, USA.
authors.forename: Siwen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Purdue University, BCHM 305, 175 S. University Street, West Lafayette, IN 47907, USA.
authors.forename: Wai Kit
authors.initials: WK
authors.lastname: Ma
authors.affiliation: Department of Biological Sciences, 5047 Gullen Mall, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Nadra
authors.initials: N
authors.lastname: Al Husini
authors.affiliation: Department of Biological Sciences, 5047 Gullen Mall, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Zuzer
authors.initials: Z
authors.lastname: Dhoondia
authors.affiliation: Department of Biological Sciences, 5047 Gullen Mall, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Athar
authors.initials: A
authors.lastname: Ansari
authors.affiliation: Department 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.
authors.forename: Pete E
authors.initials: PE
authors.lastname: Pascuzzi
authors.affiliation: Department 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.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Tran
mesh_terms: D000222:Adaptation, Physiological; D042002:Chromatin Assembly and Disassembly; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics; D005690:Galactose / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D005810:Multigene Family; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016914:Ribonuclease H / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: C065455:CYC8 protein, S cerevisiae; D004271:DNA, Fungal; C063494:HPR1 protein, S cerevisiae; D009687:Nuclear Proteins; D012331:RNA, Fungal; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D016914:Ribonuclease H; C078856:ribonuclease HI; C438898:Dbp2 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D005947:Glucose; D005690:Galactose
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