Exploring 3D miRNA networks during cellular aging.

衰老是当代研究的重点之一，研究衰老的主要挑战可以说是将其原因与不可避免地伴随它的大量变化区分开来。为了实现这一区分，我们建议有必要摆脱人类染色体的线性观点。相反，人类基因组应该在所有四个维度上进行研究：三维空间和时间。在这里，我们将研究包装到年轻细胞与老年细胞核中的人类DNA的功能相互作用，重点是非编码调节因子，如已知在衰老中起作用的microRNA。最近，我们报道了活跃的人类microRNA在转录热点（转录工厂）周围形成专门的拓扑网络。这种专门化为微小RNA与其靶基因之间的相互作用提供了充足的时间和空间机会，但迄今为止尚未研究过这种共转录相互作用。破译这些以microRNA为中心的网络的基本参与规则，为识别衰老的致病调节因子提供了一种新的方法，从长远来看，这些规则可以用来调节它们的功能输出。

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.