The biological functions of miRNAs: lessons from in vivo studies

Abstract

Despite their clear importance as a class of regulatory molecules, pinpointing the relevance of individual miRNAs has been challenging. Studies querying miRNA functions by overexpressing or silencing specific miRNAs have yielded data that are often at odds with those collected from loss-of-functions models. In addition, knockout studies suggest that many conserved miRNAs are dispensable for animal development or viability. In this review, we discuss these observations in the context of our current knowledge of miRNA biology and review the evidence implicating miRNA-mediated gene regulation in the mechanisms that ensure biological robustness.

Keywords: animal models; buffering; miRNAs; network motifs; paralogs.

Figure 1. miRNAs participate in mechanisms of biological robustness

(A)miRNAs are common features of network motifs, some of which are represented here. (B) Regulation of transcripts by miRNAs can be important to ensure robust cell fate decisions by keeping expression levels of a particular gene below a decision threshold (red lines). In the absence of a miRNA, the expression of the gene becomes unbuffered (blue lines), and can lead to ectopic cell fate decisions in a fraction of the population due to stochastic fluctuations in transcript levels. (C) Schematic representation of miR-7's role in the differentiation of photoreceptor cells in Drosophila. Panel (B) and (C) of this figure are inspired by illustrations from [89] and [142], respectively.

Figure I. Overview of protein complexes implicated in miRNA-mediated gene silencing and their effect on mRNA levels and translation efficiency