On cross-conditional and fluctuation correlations in competitive RNA networks

In competitive endogenous RNA (ceRNA) networks, different mRNAs targeted by the same miRNA can 'cross-talk' by absorbing miRNAs and relieving repression on the other mRNAs. This creates correlations in mRNA expression even without direct interaction. Most previous theoretical study of cross-talk has focused on correlations in stochastic fluctuations of mRNAs around their steady state values. However, the experimentally known examples of cross-talk do not involve single-cell fluctuations, but rather bulk tissue-level changes between conditions, such as due to differentiation or disease. In our study, we quantify for the first time both fluctuational and cross-conditional cross-talk in chemical kinetic models of miRNA-mRNA interaction networks. We study the parameter regions under which these different types of cross-talk arise, and how they are affected by network structure.