The predictive power of brain mRNA mappings for in vivo protein density: A positron emission tomography correlation study

Substantial efforts are being spent on postmortem mRNA transcription mapping on the assumption that in vivo protein distribution can be predicted from such data. We tested this assumption by comparing mRNA transcription maps from the Allen Human Brain Atlas with reference protein concentration maps acquired with positron emission tomography (PET) in two representative systems of neurotransmission (opioid and serotoninergic). We found a tight correlation between mRNA expression and specific binding with 5-HT_1A receptors measured with PET, but for opioid receptors, the correlation was weak. The discrepancy can be explained by differences in expression regulation between the two systems: transcriptional mechanisms dominate the regulation in the serotoninergic system, whereas in the opioid system proteins are further modulated after transcription. We conclude that mRNA information can be exploited for systems where translational mechanisms predominantly regulate expression. Where posttranscriptional mechanisms are important, mRNA data have to be interpreted with caution. The methodology developed here can be used for probing assumptions about the relationship of mRNA and protein in multiple neurotransmission systems.