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Neurotargeting

Current research projects

1. mRNP complexes

The levels of specific proteins in eukaryotic cells are adjusted under various physiological conditions, typically changing e.g. during cell division and in response to external or internal signals.

Failures in these processes have serious effects, for instance, leading to the transformation of cells into cancer cells. Importantly, mRNA-binding proteins control such changes in gene expression by regulating the activity, abundance, and stability of mRNAs present in mRNP complexes which are dynamic structures. Certain mRNA-binding proteins act as trans-acting proteins and organise mRNAs into functionally related subsets by binding to specific cis-acting sequences/structures mainly found within the UTRs of the mRNAs, while others participate in forming mRNP complexes through protein-protein interactions. We have a long-term interest in the composition and dynamics of mRNP complexes, and their role in the regulation of gene expression in normal and transformed cells.

 

2. The role of Annexin A2 in mRNP complexes

Annexin A2 may function as a trans-acting protein in specific mRNP complexes since it has been identified as a mRNA-binding protein.

We were the first to show that Annexin A2 acts as an mRNA-binding protein associated with a specific subpopulation of mRNPs linked to the cytoskeleton.

Furthermore, we have identified annexin A2 and c-myc mRNAs as specific Annexin A2-binding mRNAs. In both cases the protein binds to a ~100 nt region in the 3’-UTRs that evidently contains a stem-loop structure. We have mapped the mRNA-binding site of Annexin A2 to helices C-D in its domain IV (see link).

The interaction is Ca2+-dependent and involves initial electrostatic interactions between Lys residues in the protein and the mRNA phosphate backbone. The aim is to understand the function of this interaction and how it is regulated.