RNA aptamers as sensors for the miR200-family of micro RNAs

RNAs are not merely messengers (mRNA) or infrastructural components (rRNA, tRNA) in the flow of the genetic information from genes to proteins, but play a pivotal role in numerous cellular key processes. For example micro RNAs (miRs) are a family of non-coding RNAs that impact on all aspects of cellular functions by negatively regulating gene expression. Alterations in the expression and processing of miRs have been associated with disease phenotypes. Particular the miR200-family of miRs was shown to play a critical role in tumorigenesis, cancer drug resistance and they have been suggested as potential diagnostic and prognostic biomarkers in cancer. In order to understand the underlying mechanisms and connections between RNA dynamics and functions, detangling of the complex spatio-temporal dynamics of RNAs is of great importance. Therefore fluorescent RNA reporters, so called fluorescent light-up aptamers (FLAPs) have been developed. These nanoagents are based on small molecule dyes binding to structured RNAs, resulting in strong enhancement of the intrinsically very weak fluorescence of the dye. They have been used as tags to image transcripts and RNAs, as well as to detect metabolites in cells. In addition FRET-based methods using these RNA-based nano-reporters were recently reported for the analysis of RNA interactions and to track mRNA and small non-coding RNAs, respectively.

My research group is focused on the structure-function relationship of nucleic acids, investigating RNA/DNA-protein and RNA-small molecule interactions. Within the current project we plan to develop a detection system, based on genetically encoded and circularised FLAPs to monitor the spatial-temporal intracellular concentration and distribution of the miR200-family of RNAs in human cells.