RNA-association can confer targeting specificity to protein complexes and trigger their assembly into dedicated compartments. Sex chromosomes represent a prime example, but their rapid evolutionary turnover imposes exceptional challenges for mechanisms like dosage compensation (DC), which require their specific recognition. Here, we show that a rapidly evolving, low-complexity domain (CTD) of MSL2 renders its targeting to the Drosophila X chromosome sensitive to roX RNAs. Cross-species functional analyses in Drosophila and mammalian cells reveal the critical importance of the roX-MSL2CTD interplay for dosage compensation in vivo. We demonstrate that in presence of the Drosophila MSL2CTD, cis-expression of roX is sufficient to nucleate functional DC in mammalian cells. Surprisingly, this occurs without high affinity sites, indicating that the condensating nature of the roX-MSL2CTD, rather than DNA motifs, function as targeting determinants. Our studies establish principles by which ncRNAs can repurpose an evolutionary ancient expression regulator to selectively target a single chromosome. SOURCE: Asifa Akhtar (akhtarlab_data@ie-freiburg.mpg.de) - Akhtar Lab Max Planck Institute of Immunobiology and Epigenetics

Pluto Bioinformatics

GSE129831: Outcomes of MSL2 domain-swap mutation in mouse embryonic stem cells