Complexities of post-transcriptional regulation and the modeling of ceRNA crosstalk

ABSTRACTControl of gene and protein expression is required for cellular homeostasis and is disrupted in disease. Following transcription, mRNA turnover and translation is modulated, most notably by microRNAs (miRNAs). This modulation is controlled by transcriptional and post-transcriptional events that alter the availability of miRNAs for target binding. Recent studies have proposed that some transcripts – termed competitive endogenous RNAs (ceRNAs) – sequester a miRNA and diminish its repressive effects on other transcripts. Such ceRNAs thus mutually alter each other’s abundance by competing for binding to a common set of miRNAs. Some question the relevance of ceRNA crosstalk, arguing that an individual transcript, when its abundance lies within a physiological range of gene expression, will fail to compete for miRNA binding due to the high abundance of other miRNA binding sites across the transcriptome. Despite this, some experimental evidence is consistent with the ceRNA hypothesis. In this review, we ...