Small molecule manipulation of microRNA biogenesis: application to microRNAs linked to chronic diseases

Overview

Access to the information stored in our genomes is tightly controlled. One recently identified regulatory mechanism involves RNA, a versatile biological polymer related to DNA . Cells can produce small RNA molecules that can ‘interfere’ with physiological processes by controlling the production of effector proteins. Numerous regulatory RNA molecules (called microRNAs due to their small size) have been identified in humans and they have been linked to fundamental biological processes such as development, proliferation, differentiation and cell death. Their central importance is highlighted by the fact that many microRNAs are implicated in cancers.

Cells synthesize each microRNA using the same machinery. A great deal is known about microRNA biogenesis, but many critical questions remain unanswered. We aim to determine the common and unique themes underpinning microRNAs synthesis. This information will drive the design of molecules that inhibit the biosynthesis of microRNAs implicated in cancers and other diseases. In this preliminary study, we propose to implement a recently reported method for producing samples of microRNAs. This technique will greatly enhance our ability to characterise and manipulate microRNA function. Using this approach we will produce samples of disease-related microRNAs for use in the hunt for small molecules that selectively control their synthesis.

Outputs

Grants

• Michael Plevin, BBSRC, Characterisation of a new mechanism of regulation for HIFI and the hypexic response, £84,717