Multifunctional Regulatory Factor

Supervisor: Professor Rick Nicholson

Project Summary

In our ongoing study of the regulation of the corticotropin releasing hormone (CRH) gene we have identified a novel protein capable of binding to the cAMP regulatory element (CRE), found in the CRH promoter as well as many other gene promoters. This protein also possesses features suggesting a role in RNA processing. Therefore, this protein has the potential to function both as a DNA binding transcription regulatory protein and as a RNA binding protein involved in RNA splicing. We have named this protein CREAP, for CRE Associated Protein.

The regulatory proteins that modulate gene transcription and RNA processing events have historically been thought to function in one event or the other but not both. Recent research indicates that substantial cross-talk occurs between transcriptional and post-transcriptional processes. Indeed, an increasing number of proteins appear to be multifunctional, participating in both transcriptional and post-transcriptional events.

We will expand scientific knowledge in this emerging area by characterising the functions of this protein. The CREAP protein has the ability to link transcriptional and post-transcriptional regulatory events. Alternative splicing is a potential feature of the majority of mammalian genes, and an understanding of the mechanisms involved is essential to eukaryotic biology.

In this project we will perform structure function studies of CREAP to understand how it functions as a DNA binding transcription factor. Simultaneously we will perform studies to understand how CREAP functions as an RNA binding factor involved in RNA splicing.