Coupling transcriptional and post-transcriptional miRNA regulation in the control of cell fate

miRNAs function as a critical regulatory layer in development, differentiation, and the maintenance of cell fate. Depletion of miRNAs from embryonic stem cells impairs their differentiation capacity. Total elimination of miRNAs leads to premature senescence in normal cells and tissues through activation of the DNA-damage checkpoint, whereas ablation of miRNAs in cancer cell lines results in an opposite effect, enhancing their tumorigenic potential. Here we compile evidence from the literature that point at miRNAs as key players in the maintenance of genomic integrity and proper cell fate. There is an apparent gap between our understanding of the subtle way by which miRNAs modulate protein levels, and their profound impact on cell fate. We propose that examining miRNAs in the context of the regulatory transcriptional and post-transcriptional networks they are embedded in may provide a broader view of their role in controlling cell fate.