I have a transgenic mouse model that shows 40 fold increase in mRNA of my gene of interest, but only 20% increase in protein levels (very little over-expression). This is an inducible model used for conditional expression in the heart that has been used for other genes successfully, so I don't anticipate there is a problem with the mouse. My protein of interest is tagged so I can clearly distinguish between endogenous and transgenic. I'm leaning towards some kind of tranlational inhibition or protein degradation. I would appreciate any insights.
Your protein might be regulated by miRNA at the translation level
It may depend on how stable the mRNA is. Stability of the RNA is often ignored, but varies widely and the amount of mRNA is not a predictor of protein level many times. If the mRNA has a long half-life, a small amount can produce a lot of protein, and vice versa. Stability depends on numerous factors, and an mRNA from a cDNA clone may be quite different than the endogenous mRNA in this.
It probably also depends on how fast your proteins degrade. Some proteins degrade in the matter of minutes.
See this article: "How fast do RNAs and proteins degrade?"
http://book.bionumbers.org/how-fast-do-rnas-and-proteins-degrade/
Don't you think the tagged protein undergoes degradation while the native one does not?
Thank you for the possible answers. One interesting thing I have noticed is that the total amounts (endogenous + transgenic) seem to decrease over time of induction. At three weeks I have between 100-120% of endogenous levels of control mice, but at 10 weeks, I have sometimes as low as 60% of endogenous levels of control mice. Also, the majority of the proteins shifts from mostly endogenous at earlier time points to 50% or more transgenic at longer time points. To me, this seems to suggest some kind of response at the translation level. All time points show the same levels of mRNA.
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