SMN1 - Spinal Muscular Atrophy

There are a wide array of possibilities and avenues that can be explored concerning the SMN-1 gene and its functions. In order to understand more particularly it functions, I believe that the protein interaction networks should be explored more fully.  There are a host of proteins that interact with survival of motor neuron protein, but their function and the full interaction map is not complete.

I propose that a more in depth study be performed to expand the protein interaction network.  This could be done most straightforwardly with the Y2H experiments.  This would hopefully reveal more relevant interactions, although the error rate of Y2H means that it will be difficult to attain sure data.  Of course, this information can be cross-referenced with other tests to get better results.  Once we gain more information about the proteins that SMN interacts with we can understand the SMN-complex better and realize the exact way in which the lack of smn leads to spinal muscular atrophy.  It would be useful to do these tests in a variety of tissues in order to determine which proteins are interacting in particular tissues.

Something that surprised me was that although SMN is expressed in all tissue types, when it is mutated its effect is only really seen in the spinal cord.  I think that there are two possibilities.  Either SMN is expressed at greater levels in the spinal cord or there is a particular protein that must be created in order for proper function of anterior horn cells in the spine.  I think that the Y2H tests that I suggested earlier would be useful in determining this.  It would also be useful to perform microarray tests that would illustrate how SMN is expressed in different tissues.  This would hopefully settle this problem and lead to a better understanding of the SMN function.

Not only will understanding SMN function allow us to develop strategies to cure SMA, it will also lead to a general increase in our knowledge of biological processes.  If we understand the function of SMA we will be able to understand the biogenesis of snRNP and subsequently the formation of the spliceosome.  Knowledge of this sort will have many applications beyond spinal muscualar atrophy.