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Tandem Stem-Loops in roX RNAs Act Together to Mediate X Chromsome Dosage Compensation in Drosophila

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Ilik,  Ibrahim Avsar
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Georgiev,  Plamen
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Toscano,  Sarah
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Akhtar,  Asifa
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Ilik, I. A., Quinn, J., Georgiev, P., Tavares-Cadete, F., Maticzka, D., Toscano, S., et al. (2013). Tandem Stem-Loops in roX RNAs Act Together to Mediate X Chromsome Dosage Compensation in Drosophila. Molecular Cell, 51, 156-173.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-88EA-5
Abstract
Dosage compensation in Drosophila is an epigenetic phenomenon utilizing proteins and long noncoding RNAs (lncRNAs) for transcriptional upregulation of the male X chromosome. Here, by using UV crosslinking followed by deep sequencing, we show that two enzymes in the Male-Specific Lethal complex, MLE RNA helicase and MSL2 ubiquitin ligase, bind evolutionarily conserved domains containing tandem stem-loops in roX1 and roX2 RNAs in vivo. These domains constitute the minimal RNA unit present in multiple copies in diverse arrangements for nucleation of the MSL complex. MLE binds to these domains with distinct ATP-independent and ATP-dependent behavior. Importantly, we show that different roX RNA domains have overlapping function, since only combinatorial mutations in the tandem stem-loops result in severe loss of dosage compensation and consequently male-specific lethality. We propose that repetitive structural motifs in lncRNAs could provide plasticity during multiprotein complex assemblies to ensure efficient targeting in cis or in trans along chromosomes.