tl;dr: I don’t know why people say that RNA doesn’t correlate with protein. There are different contexts to this question, and some recent experiments may make the question a bit confusing, but overall, I’m pretty sure that most of the time, if you increase the amount of RNA for a given gene, you will end up with more of the protein encoded by that gene. I’m sure there are counter-examples, though–if you know of any, please fill me in.
In our group, when we present work on RNA abundances, we are often faced with the question: “Well, what about the protein?” (fair enough). This is usually followed by the statement “Because of course it is well known that RNA doesn’t correlate with protein.” Umm, what?
I have to say that I’m a bit puzzled by this bit of apparently obvious and self-evident truth. I thought that most people accept that the central dogma of DNA to RNA to protein is a pretty solid fact in most cases. So… if you have more RNA, that should lead to more protein, right? Shouldn’t that be the null hypothesis?
Apparently this notion has been around for a long time, though nowadays it is perhaps a bit more conceptually confusing due to a few recent results. Perhaps the biggest one was the Schwanhausser paper in which they compare RNA-seq to mass-spec and show that there is a distinct lack of correlation between mean RNA levels and mean protein levels across all genes (also the Weissman ribosome profiling paper). What this means, on the face of it, is that even if gene A produces more RNA than gene B, then it may be the case that there is more protein B than protein A. Fine. There are differences in protein translation rate and degradation rate, leading to these differences, no surprises there. Plus, Mark Biggins and Allan Drummond make the point that any measurement noise will lead to decorrelation even if things are very correlated, and their reanalyses seem to indicate that the correlation between RNA and protein may actually be considerably higher than initially reported.
The next example that’s a bit closer to home for me is whether RNA levels and protein levels correlate, even for the same gene, across single cells. Here, it gets a bit more complex, and one might expect a variety of behaviors depending on the burstiness of transcription, degradation rate of the RNA and the degradation rate of the protein. Experimentally, there are some cases in which the RNA and protein of a particular gene do not correlate in single cells (Taniguchi et al. Science 2010 is a particularly good example). This may be due to long protein half-life, which effectively smooths over RNA fluctuations. In our PLOS 2006 paper (Fig. 7), we showed that there can be a strong correlation between RNA and protein when the protein degrades fast, and that correlation goes down a lot when the protein degrades more slowly.
And of course there’s the whole world of post-translational modifications, like during the cell cycle, etc., in which protein activity and potentially levels change independent of transcript abundance. Well, dunno what to say about that, I’m biased to just think about RNA. :)
Nevertheless, overall, I think it’s pretty safe to assume most of the time that if you increase RNA abundance for a particular gene, you will end up with more of the encoded protein. I think that should be the null hypothesis. If anyone knows of any counterexamples, please let me know.
Oh, and by the way, in case you’re wondering, transcription also correlates with RNA.