If there is low correlation between gene expression and protein levels, why are we still analyzing and extrapolating mRNA level to proteins?

Question

[Diwan]

Hello,

I frequently hear (and read in papers) that there is a low correlation between gene expression and protein levels. But I don't get a good answer as to why we still do gene expression analysis.

Is this a valid reason: (Given that we know the limitation of the approach) we still have that the potential to get new biological insight/discovery.

Is it easier and cheaper to screen the genome-wide expression and then look for specific protein than to screen the entire proteome?

Or is there any other reason.

Thanks
Diwan

Answer 1

[Devon Ryan]

The reason you listed is certainly one of the good ones. The reality is also that looking at RNA levels is currently easier and cheaper than trying to look directly at proteins in a high throughput manner. One can use mass spec. or use a protein array to look at protein levels, but these aren't terribly cheap technologies. Not to mention that there's the added difficulty that proteins can be difficult to solublize due to being membrane-bound or tethered or so on. I fully expect that technology will advance such that we will just directly look at protein, but for the most part we aren't there yet.

Answer 2

[DG]

As Devon pointed out cost is really the big driving factor as well as technology. It is cheaper/easier to look at RNA levels on genome-wide scales and determine levels of transcription compared to doing genome-wide screens of protein levels. In my (limited) experience with protein mass-spec data it is also less reliable in terms of quantifying absolute protein levels for a variety of reasons technically.

Also, from my understanding of the papers discussing correlations between mRNA and protein levels is that the lack of correlation is often a matter of the amounts not correlating strongly versus the direction. And some of this is being driven by factors that are also discoverable within the RNA experiment itself. An example would be when a transcript is upregulated but so are miRNAs that target it.