Study the targetome structures of OncomiR 34a to reveal the regulatory mechanism

MicroRNAs (miRs) are dysregulated in over half of all cancers and numerous other diseases.

The efficiency of miRs´ regulation is primarily predicted based upon a 6-8 nucleotide base-paired region known as the seed, within the overall 20-25 nucleotide length of the miR. However, this predictive capacity is often lacking.

Our aim is to investigate the structure-function relationship of the miR-34a targetome to enhance the predictive accuracy of miR-34a down-regulation, a crucial factor in cancer regulation.

Building upon our initial findings, which uncovered key structural features, such as the miR bulge or the occluded seed rescue mechanism, we propose a series of high-throughput experiments to elucidate the structural parameters, thus improving predictive capabilities.

Through the integration of RNA sequencing, mass spectrometry, RNA structural probing, and fluorescent affinity probing across all mRNA targets of miR-34a, coupled with advanced computational analysis and modeling, we aim to establish hierarchical rules for miR-34a targeting.

The successful prediction will not only enhance the reliability and efficiency of microRNA/siRNA-based molecular biology experiments but will also facilitate the design of miR-based drugs with significantly enhanced specificity.