Li Jianjian, Xu Shuyang, Liu Zicong, Yang Liuyi, Ming Zhe, Zhang Rui, Zhao Wenjuan, Peng Huipai, Quinn Jeffrey J, Wu Manyin, Geng Yushan, Zhang Yuying, He Jiazhi, Chen Minghai, Li Nan, Shao Ning-Yi, Ma Qing
Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Faculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen, China.
Nat Commun. 2025 Jan 2;16(1):155. doi: 10.1038/s41467-024-55711-y.
Long noncoding RNAs known as roX (RNA on the X) are crucial for male development in Drosophila, as their loss leads to male lethality from the late larval stages. While roX RNAs are recognized for their role in sex-chromosome dosage compensation, ensuring balanced expression of X-linked genes in both sexes, their potential influence on autosomal gene regulation remains unexplored. Here, using an integrative multi-omics approach, we show that roX RNAs not only govern the X chromosome but also target genes on autosomes that lack male-specific lethal (MSL) complex occupancy, together with Polycomb repressive complexes (PRCs). We observed that roX RNAs colocalize with MSL proteins on the X chromosome and PRC components on autosomes. Intriguingly, loss of roX function reduces X-chromosomal H4K16ac levels and autosomal H3K27me3 levels. Correspondingly, X-linked genes display reduced expression, whereas many autosomal genes exhibit elevated expression upon roX loss. Our findings propose a dual role for roX RNAs: activators of X-linked genes and repressors of autosomal genes, achieved through interactions with MSL and PRC complexes, respectively. This study uncovers the unconventional epigenetic repressive function of roX RNAs with PRC interaction.
被称为roX（X染色体上的RNA）的长链非编码RNA对果蝇的雄性发育至关重要，因为它们的缺失会导致从幼虫后期开始的雄性致死。虽然roX RNA因其在性染色体剂量补偿中的作用而被认可，可确保X连锁基因在两性中平衡表达，但其对常染色体基因调控的潜在影响仍未被探索。在这里，我们使用综合多组学方法表明，roX RNA不仅控制X染色体，还靶向常染色体上缺乏雄性特异性致死（MSL）复合物占据的基因，以及多梳抑制复合物（PRC）。我们观察到roX RNA与X染色体上的MSL蛋白和常染色体上的PRC成分共定位。有趣的是，roX功能的丧失会降低X染色体上的H4K16ac水平和常染色体上的H3K27me3水平。相应地，X连锁基因的表达降低，而许多常染色体基因在roX缺失时表现出表达升高。我们的研究结果提出了roX RNA的双重作用：分别通过与MSL和PRC复合物相互作用，作为X连锁基因的激活剂和常染色体基因的抑制剂。这项研究揭示了roX RNA与PRC相互作用的非常规表观遗传抑制功能。
