I have seen a lot of research into molecular mechanisms of diseases/phenotypes use measures of RNA as a 'proxy' for the level of protein available in the cell. Is this actually valid?
My problem with the assumption that RNA levels correlate with that of the active product (i.e. the protein) is that a lot of post translational regulation occurs, including co-factor binding and phosphorylation, to name but 2. Does anyone know of any studies that have looked into the correlation between RNA levels and protein levels, and separately into the correlations between RNA levels and active protein?
It makes sense to me that RNA would correlate with protein certainly, but whether this relates to the proteins active function is what I wonder - i.e. there could be a pool that is replenished as and when the protein levels drop, but the proteins are only actually active for short periods in response to specific stimuli. So, does anyone know of any studies that have looked into the correlation between RNA levels and protein levels, and separately into the correlations between RNA levels and active protein?
I have not accepted any answers as yet because none address my question about levels of protein activation, but I concede to Daniel's excellent point that proteins are not all activated in the same way; some are constantly active, some require phosphorylation (multiple sites?), some binding partners... etc! So a study looking at 'global' activation is not yet possible. Yet I was hoping that someone may have read some specific examples.
I today found an unpublished review by Nancy Kendrick of 10 studies that have looked at the correlation between mRNA and protein abundance - still not relating to activation. However she finishes the paper as follows;
The conclusion from the ten examples listed above seems inescapable: mRNA levels cannot be used as surrogates for corresponding protein levels without verification.
If this is her conclusion about protein levels, then any correlation between protein activation and mRNA abundance seems unlikely (as a rule. Some protein levels do correlate with the RNA - see the paper).
I am still interested in any answers that give any information about specific examples of protein activation and mRNA levels - it seems highly unlikely there are no such studies, but I have been as yet unable to find any!