Hi,
Usually when protein level increase is detected, the transcript level is usually unaffected or increased depending on whether it is translational or transcriptional regulation. However, I have encountered a scenario where my protein of interest increases after a stress stimulus but shows downregulation at mRNA level. Is this possible? I mean has anyone seen this or read a paper where authors found similar thing.
Thanks
I’m not aware of any examples in the literature, but sounds like an intriguing result. It could be explained by stress either decreasing proteasomal degradation of the protein (similar to how hypoxia causes stabilization of HIF-1) or increasing/enhancing translation of the mRNA (seen in response to stress: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002527). The decrease in mRNA level is surprising, but could be part of some regulatory feedback loop. ie. the protein levels increase, but the transcript is decreased (could be decreased transcription or increased degradation) which would facilitate recovery of the system following stress removal. The protein would then be degraded or translated normally, decreasing levels. The reduced pool of mRNA would ensure that levels of this protein of interest don’t get too high and I suppose create a window of time for the system to reset. In support of this idea, on average protein half-lifes are ~46hr while mRNA half-lifes are 2.6-7 hrs on average (http://www.nature.com/nrg/journal/v13/n4/full/nrg3185.html)
Feedback inhibition of transcription is a common control mechanism in homeostasis and metabolic pathways. Regulation can be direct (e.g., GalS repressor control of the gal operon in E. coli) or indirect (the circadian timer Period acting through the Clock/Cycle transcription factors that govern Period expression). Another explanation for the observed phenomenon is translation-coupled mRNA turnover.
While the general trend is a positive correlation between transcript and protein levels, see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654667/ for a recent review that includes numerous exceptions.