Extensive ceRNA–ceRNA interaction networks mediated by miRNAs regulate development in multiple rhesus tissues

Abstract

Crosstalk between RNAs mediated by shared microRNAs (miRNAs) represents a novel layer of gene regulation, which plays important roles in development. In this study, we analyzed time series expression data for coding genes and long non-coding RNAs (lncRNAs) to identify thousands of interactions among competitive endogenous RNAs (ceRNAs) in four rhesus tissues. The ceRNAs exhibited dynamic expression and regulatory patterns during each tissue development process, which suggests that ceRNAs might work synergistically during different developmental stages or tissues to control specific functions. In addition, lncRNAs exhibit higher specificity as ceRNAs than coding-genes and their functions were predicted based on their competitive coding-gene partners to discover their important developmental roles. In addition to the specificity of tissue development, functional analyses demonstrated that the combined effects of multiple ceRNAs can have major impacts on general developmental and metabolic processes in multiple tissues, especially transcription-related functions where competitive interactions. Moreover, ceRNA interactions could sequentially and/or synergistically mediate the crosstalk among different signaling pathways during brain development. Analyzing ceRNA interactions during the development of multiple tissues will provideinsights in the regulation of normal development and the dysregulation of key mechanisms during pathogenesis.