Question: What exactly are you finding out about SMA?

Judith Sleeman answered on 18 Jun 2012:

The work I have just published looked at how RNA splicing factors move around inside the nucleus. A few years ago, a group in the USA published results that showed widespread problems with RNA splicing in mouse models of SMA. They suggested that there are some special messenger RNAs that are needed by motor neurons (the cells that are damaged in SMA patients) that aren’t spliced properly in people with SMA but they haven’t found them yet. The way RNA splicing is organised in the nucleus seems a bit hap-hazard (although I promise you, it isn’t really!): all of the proteins needed for splicing just sort of diffuse around in the nucleus unless they ‘meet’ an RNA that needs to be spliced. If this happens, they stop for a while. So, slowly moving splicing factors mean that splicing can happen properly and quickly moving splicing factors suggest a problem. We saw that, in SMA cells, splicing factors move around more quickly. So, too little SMN make splicing factors move too quickly and this might explain why there are problems with splicing in the SMA mice. Of course, how important this turns out to be will depend on whether the splicing problems can be proved to be what causes cell damage in SMA. If not, well, at least we will know why the scientists in the USA got the results that they got!

The experiments I’m doing now are looking at some tiny structures containing splicing factors that move around really quickly in the cytoplasm of brain cells. I’m not sure what they are yet, but they contain the SMN protein as well. They only seem to contain two or three types of splicing factor, so they can’t be for splicing RNA. They might be important: they might not! Time (and, I hope, my experiments) will tell…