Ribonomic approaches to identify protein-mRNA and microRNA-mRNA interactions: Implications for drug design

Preclinical Research Posttranscriptional regulation of gene expression is now recognized to play a large role in physiological and pathological processes. Through interactions with messenger ribonucleic acid (mRNA), RNA-binding proteins (RBPs) and microRNAs (miRNAs) can alter mRNA stability or translation. Aberrant function of these pathways may play a role in inflammatory diseases and cancer, making these attractive therapeutic targets. miRNAs and some RBPs, such as tristetraprolin (TTP), destabilize mRNA and may inhibit translation. Other RBPs, such as HuR, may increase mRNA stability to upregulate gene expression. Each RBP or a single miRNA has the potential to regulate multiple functionally related targets by binding to specific sequences or motifs on mRNA. Identification of these regulatory interactions has become a key step in understanding how gene expression is controlled and in designing drugs to target these interactions in disease. A number of ribonomic techniques have been developed to accurately identify RBP-mRNA and miRNA-mRNA binding interactions, including immunoprecipitation and affinity purification techniques combined with microarray technology and high-throughput deoxyribonucleic acid (DNA) sequencing. Information gained from these approaches can be used to design agents that mimic or inhibit these regulatory interactions and thus represents a novel strategy for the treatment of disease.