Research

in the Passmore Lab

 

The Passmore laboratory uses a hybrid approach to study the structure and function of multi-protein complexes involved in the regulation of mRNA polyadenylation and deadenylation. Eukaryotic genes are normally transcribed as pre-mRNAs that must be processed before they are exported from the nucleus and translated into proteins. The 3´-end of the pre-mRNA undergoes cleavage and addition of a poly(A) tail. Several protein factors are required to co-ordinate the 3´-end processing reactions, and to facilitate communication with the transcription and splicing machinery. In yeast this includes a large multi-protein complex called Cleavage and Polyadenylation Factor (CPF).

The poly(A) tail is required for export of the mRNA into the cytoplasm. It also enhances mRNA stability and stimulates translation, and its length can be regulated to influence these functions. For example, shortening of the poly(A) tail can decrease the efficiency of translation to control gene expression in some cases, and is the first step in mRNA turnover. The main deadenylase activities are found within the evolutionarily conserved, 1 MDa Ccr4-Not complex and the Pan2–Pan3 complex.


By understanding the structure and mechanisms of these complexes, we will gain insight into the regulation of mRNA polyadenylation and gene expression.

Macromolecular machines involved in regulation of mRNA 3´ ends

Macromolecular machines involved in other cellular processes

We are also interested in protein complexes involved in other cellular processes including protein translation, signalling and DNA repair. We are studying the Fanconi Anaemia core complex, a multi-protein E3 monoubiquitin ligase involved in the repair of DNA interstrand crosslinks, in collaboration with KJ Patel.