title: Dicer-microRNA-Myc circuit promotes transcription of hundreds of long noncoding RNAs.
abstract: Long noncoding RNAs (lncRNAs) are important regulators of cell fate, yet little is known about mechanisms controlling lncRNA expression. Here we show that transcription is quantitatively different for lncRNAs and mRNAs--as revealed by deficiency of Dicer (Dcr), a key RNase that generates microRNAs (miRNAs). Dcr loss in mouse embryonic stem cells led unexpectedly to decreased levels of hundreds of lncRNAs. The canonical Dgcr8-Dcr-miRNA pathway is required for robust lncRNA transcriptional initiation and elongation. Computational and genetic epistasis analyses demonstrated that Dcr activation of the oncogenic transcription factor cMyc is partly responsible for lncRNA expression. A quantitative metric of mRNA-lncRNA decoupling revealed that Dcr and cMyc differentially regulate lncRNAs versus mRNAs in diverse cell types and in vivo. Thus, numerous lncRNAs may be modulated as a class in development and disease, notably where Dcr and cMyc act.
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Grace X Y
authors.initials: GX
authors.lastname: Zheng
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Do
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Dan E
authors.initials: DE
authors.lastname: Webster
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Khavari
authors.affiliation: 1] Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA. [2] Howard Hughes Medical Institute, Stanford, California, USA.
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D055786:Gene Knockout Techniques; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases