Challenges in microRNAs’ targetome prediction and validation

MicroRNAs (miRNAs) are small RNA molecules with important roles in post-transcriptional regulation of gene expression. In recent years, the predicted number of miRNAs has skyrocketed, largely as a consequence of high-throughput sequencing technologies becoming ubiquitous. This dramatic increase in miRNA candidates poses multiple challenges in terms of data deposition, curation, and validation. Although multiple databases containing miRNA annotations and targets have been developed, ensuring data quality by validating miRNA-target interactions requires the efforts of the research community. In order to generate databases containing biologically active miRNAs, it is imperative to overcome a multitude of hurdles, including restricted miRNA expression patterns, distinct miRNA biogenesis machineries, and divergent miRNA-mRNA interaction dynamics. In the present review, we discuss recent advances and limitations in miRNA prediction, identification, and validation. Lastly, we focus on the most enriched neuronal miRNA, miR-124, and its gene regulatory network in human neurons, which has been revealed using a combined computational and experimental approach.