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Genes Dev. 2016 Jan 15;30(2):191-207. doi: 10.1101/gad.272187.115.

Rapid evolutionary turnover underlies conserved lncRNA-genome interactions.

Author information

1
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;
2
Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California 94305, USA;
3
Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg im Breisgau, Germany.

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.

KEYWORDS:

ChIRP; Drosophila; RNA structure; dosage compensation; lncRNAs; roX

PMID:
26773003
PMCID:
PMC4719309
DOI:
10.1101/gad.272187.115
[Indexed for MEDLINE]
Free PMC Article

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