Tuesday, February 17, 2015
Impact of regulatory variation from RNA to Protein
Every tried to compare your mammalian transcript quantities to your protein quantities? Even if you harvest the same cell lines at the same time, if you are expecting it to match up...
The reasons why have kind of diverged more into the easier analyses, like which one is better (protein, obviously!). The question of why we have all this variation between transcript and actual protein expression levels is a much tougher question. Tough enough that the first decent swing at it made this month's Science.
In this paper from Alexis Battle, et. al., these authors take a look at gene products at three levels. They go after the messenger RNA, the ribosome profiles, and the protein quantification (using SILAC).
What did they find? Tons of stuff. Holy cow, this is the most dense 3 page paper I've dug through in quite a while. High level analysis, though? At the top, they identified something they call "cis quantitative trait loci" that appear to function to minimize the effects of differential mRNA expression at the protein level. That is, these things exist to make sure that even when the mRNA levels say "stress! make 1,000 times more of this stuff!!!" these cis things make sure that the protein copies actually produced stay within normal biological limits.
Again, this is a seriously deep paper. There are observations backed with heavy statistics on the ability to different individual sample variation at each of these levels (including SILAC!). Another interesting point of this paper is that we're looking at what can happen when these next-gen genomics scientists apply their statistics to our field...
I highly recommend you check this out!