Short stories about long RNAs
Although thousands of non-coding RNAs are encoded in mammalian genomes, their mechanisms of action are largely uncharacterized. One such ncRNA Xist mediates chromosome-wide gene silencing on one of the two X chromosomes to achieve gene expression balance between males and females. However, how a limited number of Xist molecules can mediate robust silencing of a significantly larger number of target genes (~1 Xist RNA: 10 gene targets) while maintaining specificity exclusively to genes on the X within each cell, is unclear. I will present our recent observations uncovering a spatial amplification mechanism that allows Xist to achieve these two essentials but countervailing regulatory objectives: chromosome-wide gene silencing and specificity to the X. I will discuss how this spatial amplification mechanism may be a more general mechanism by which other non-coding nuclear RNAs can balance specificity to, and robust control of, their regulatory targets. Lastly, I will show how our newly developed method RNA-DNA SPRITE can help to understand the 3D nuclear localization of these RNAs and identify their genomic targets at the genome-wide scale
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