CAREER: The Versatility of microRNA Regulation

Cornell University, Ithaca NY

Investigators

Abstract

1350659 Shen, Xiling MicroRNAs are small non-coding RNAs that bind and inactivate target messenger RNAs (mRNAs). While the extensive roles of microRNAs in regulating cellular processes have been appreciated by now, the questions emerge as why many critical hubs in the regulatory network rely on microRNA rather than protein, and how such microRNAs manage to properly regulate genes of drastically different dynamic properties. The purpose of microRNA is often thought to fine-tune gene expression. However, a recent study has demonstrated that microRNAs can also form a binary switch to determine cell fate asymmetry, which suggests that microRNA regulation is more versatile than it was previously given credit for. This project will investigate how microRNA versatility contributes to the overall performance of the regulatory network in terms of robustness, programmability and speed. The proposed study will combine computational modeling and quantitative experiments to approach these questions from three angles: (i) Do microRNAs and proteins form specific regulatory motifs to enhance regulation dynamics? (ii) Do microRNAs target specific sets of genes for binary instead of modulatory regulation? (iii) Is microRNA regulation capable of filtering extrinsic and intrinsic cellular noise? Found in plants and animals, microRNAs add an extra layer of complexity to regulatory networks and play critical roles in development, oncogenesis, aging, etc. The proposed study will reveal the versatility of microRNAs and how they contribute to the performance of the regulatory network. This may provide an explanation as to why certain microRNAs serve as regulatory hubs while others do not. The study may also reveal the underlying mechanism that allows microRNAs to be programmable by evolution and help improve future microRNA-dependent diagnostics and therapies. Due to the interdisciplinary nature of the project, this CAREER award by the Biotechnology, Biochemical, and Biomass Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology.