Intrinsic noise of microRNA-regulated genes and the ceRNA hypothesis

TL;DR

This study uses a quantitative model to compare gene regulation by microRNAs and prokaryotic sRNAs, revealing similar noise profiles and robustness, and explores microRNA-mediated mRNA interactions and the ceRNA hypothesis.

Contribution

The paper introduces a unified model for microRNA and sRNA regulation, demonstrating their similar noise characteristics and analyzing microRNA-mediated mRNA crosstalk.

Findings

MicroRNA and sRNA regulation produce nearly identical mean expression and noise profiles.

MicroRNA-mediated mRNA interactions can be effectively measured by noise sensitivity.

The model supports experimental strategies to test the ceRNA hypothesis.

Abstract

MicroRNAs are small noncoding RNAs that regulate genes post-transciptionally by binding and degrading target eukaryotic mRNAs. We use a quantitative model to study gene regulation by inhibitory microRNAs and compare it to gene regulation by prokaryotic small non-coding RNAs (sRNAs). Our model uses a combination of analytic techniques as well as computational simulations to calculate the mean-expression and noise profiles of genes regulated by both microRNAs and sRNAs. We find that despite very different molecular machinery and modes of action (catalytic vs stoichiometric), the mean expression levels and noise profiles of microRNA-regulated genes are almost identical to genes regulated by prokaryotic sRNAs. This behavior is extremely robust and persists across a wide range of biologically relevant parameters. We extend our model to study crosstalk between multiple mRNAs that are regulated by a single microRNA and show that noise is a sensitive measure of microRNA-mediated interaction between mRNAs. We conclude by discussing possible experimental strategies for uncovering the microRNA-mRNA interactions and testing the competing endogenous RNA (ceRNA) hypothesis.