Excellence in Research: MicroRNA Detection Strategies via Exploration of Flavin Binding Allosteric Switches

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Mehnaaz F. Ali of Xavier University of Louisiana is studying the design and exploration of flavin induced allosteric aptamers with microRNA specific functional domains. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are biologically active forms of riboflavin.

These molecules play diverse and wide-ranging roles in a multitude of biological processes due to their structure and chemical versatility. The exploration of FAD and their interactions as ligands within allosteric nucleic acid probes will offer fundamental insight into their potential role as molecular switches, chemo-responsive sensors or genetic control elements.

In addition to promoting discovery in nucleic acid chemistry and sensing fields, this project (both directly and indirectly-via Dr. Ali’s teaching responsibilities and outreach program) will also promote teaching, and learning of chemistry at the middle school through undergraduate level.

RNA polymers are well known for their ability to present a range of distinct structural conformations. These molecules lend themselves to the formation of allosteric nucleic acid scaffolds with multiple binding domains. Although ubiquitous in nature, the isolation of molecules with dual-domain functionality from a random sequence population is not facile.

An approach to generating allosteric ribozymes is to utilize a mixture of modular rational design in combination with in-vitro selection strategies. To explore the utility of flavins as ligands, Dr. Ali is interested in using a combination of these existing efforts to design allosteric systems by using rational design to construct flavin dependent conformational switches, where flavin binding will lead to the formation of binding pockets using an aptamer scaffold with tailored miR binding regions.

Such forms of ‘adaptive-binding’ have traditionally been used with RNA motifs to allosterically regulate the activity of naturally occurring catalytic RNA. Together, these systems provide novel approaches to chemo-responsive sensing, particularly novel methods of allosteric aptamer development. Specifically, these studies are expected to contribute to the design of new flavin binding scaffolds for sensing microRNA.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.