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

Reut Shalgi,Moshe Oren,Varda Rotter,Yitzhak Pilpel,Ran Brosh

doi:10.18632/aging.100085

Abstract

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.

Highlights

MiRNAs are key regulators of cell fate miRNAs have emerged in the past decade as important players in numerous cellular and organismal processes in animals and plants [1]
Other studies have shown a major role for miRNAs in development, indicating that many miRNAs are upregulated during the process of embryonic stem (ES) cell differentiation ([12] and reviewed in [13])
Two principles are common to the different examples discussed above: 1. miRNAs are embedded in combined transcriptionnal/post-transcriptional Feed-Forward Loops (FFLs) that co-target many genes

Summary

Introduction

MiRNAs are key regulators of cell fate miRNAs have emerged in the past decade as important players in numerous cellular and organismal processes in animals and plants [1]. Globally avoiding regulation of gene expression by miRNAs may be one of the many ways of cancer cells to enhance their proliferation and tumorigenic potential. Several lines of evidence support the idea that proliferating cells and cancer cells in particular, find many different ways to avoid post-transcriptional regulation by miRNAs (Figure 1).

Results

Conclusion