title: Enhancer RNA facilitates NELF release from immediate early genes.
abstract: Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons. eRNAs are synthesized prior to the culmination of target gene transcription and interact with the NELF complex. Knockdown of eRNAs expressed at neuronal enhancers impairs transient release of NELF from the specific target promoters during transcriptional activation, coinciding with a decrease in target mRNA induction. The enhancer-promoter interaction was unaffected by eRNA knockdown. Instead, chromatin looping might enable eRNAs to act locally at a specific promoter. Our findings highlight the spatiotemporally regulated action mechanism of eRNAs during early transcriptional elongation.
authors.affiliation: Department of Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Schaukowitch
authors.affiliation: Department of Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111, USA.
authors.forename: Jae-Yeol
authors.initials: JY
authors.lastname: Joo
authors.affiliation: Department of Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111, USA.
authors.forename: Xihui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111, USA.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Watts
authors.affiliation: Sigma Life Science, 9186 Six Pines Drive, The Woodlands, TX 77380, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Martinez
authors.affiliation: Department of Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111, USA. Electronic address: taekyung.kim@utsouthwestern.edu.
authors.forename: Tae-Kyung
authors.initials: TK
authors.lastname: Kim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism / Q000502:physiology; D062085:RNA, Long Noncoding / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D002843:Chromatin; C582413:NELF protein, mouse; D062085:RNA, Long Noncoding; D014157:Transcription Factors; D012319:RNA Polymerase II