title: Rapid evolutionary turnover underlies conserved lncRNA-genome interactions.
abstract: Many long noncoding RNAs (lncRNAs) can regulate chromatin states, but the evolutionary origin and dynamics driving lncRNA-genome interactions are unclear. We adapted an integrative strategy that identifies lncRNA orthologs in different species despite limited sequence similarity, which is applicable to mammalian and insect lncRNAs. Analysis of the roX lncRNAs, which are essential for dosage compensation of the single X chromosome in Drosophila males, revealed 47 new roX orthologs in diverse Drosophilid species across ∼40 million years of evolution. Genetic rescue by roX orthologs and engineered synthetic lncRNAs showed that altering the number of focal, repetitive RNA structures determines roX ortholog function. Genomic occupancy maps of roX RNAs in four species revealed conserved targeting of X chromosome neighborhoods but rapid turnover of individual binding sites. Many new roX-binding sites evolved from DNA encoding a pre-existing RNA splicing signal, effectively linking dosage compensation to transcribed genes. Thus, dynamic change in lncRNAs and their genomic targets underlies conserved and essential lncRNA-genome interactions.
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California 94305, USA; Department of Bioengineering, Stanford University School of Medicine and School of Engineering, Stanford, California 94305, USA;
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Quinn
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California 94305, USA;
authors.forename: Qiangfeng C
authors.initials: QC
authors.lastname: Zhang
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg im Breisgau, Germany.
authors.forename: Plamen
authors.initials: P
authors.lastname: Georgiev
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg im Breisgau, Germany.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Ilik
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg im Breisgau, Germany.
authors.forename: Asifa
authors.initials: A
authors.lastname: Akhtar
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California 94305, USA;
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D059006:Chromosomes, Insect / Q000235:genetics / Q000378:metabolism; D004303:Dosage Compensation, Genetic / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D049750:Genome, Insect / Q000235:genetics*; D008297:Male; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D062085:RNA, Long Noncoding
keywords: ChIRP; Drosophila; RNA structure; dosage compensation; lncRNAs; roX