Exploring 3D miRNA networks during cellular aging.

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One of the major contemporary research priorities is aging, and arguably the major challenge in studying aging is distinguishing its causes from the vast number of changes that inevitably accompany it. To achieve this distinction, we propose that it is necessary to escape the linear view of human chromosomes. Instead, the human genome should be studied in all four dimensions: three-dimensional space and time. Here, we will investigate functional interactions of human DNA packed into nuclei of young versus old cells, with a focus on non-coding regulators, like microRNAs that have been known to have a role in aging. Recently we reported that active human microRNAs form specialized topological networks around transcriptional hot-spots, transcription factories. This specialization offers ample temporal and spatial opportunities for interactions between microRNAs and their target genes, and such a co-transcriptional interplay has not been studied to date. Deciphering the fundamental rules of engagement of these microRNA-centered networks offers a novel means for identifying causative regulators of aging, and in the long run these rules could be used to modulate their functional output.