How energy determines spatial localisation and copy number of molecules in neurons

Abstract

Abstract In neurons, the quantities of mRNAs and proteins are traditionally assumed to be determined by functional, electrical or genetic factors. Yet, there may also be global, currently unknown computational rules that are valid across different molecular species inside a cell. Surprisingly, our results show that the energy for molecular turnover is a significant cellular expense, en par with spiking cost, and which requires energy-saving strategies. We show that the drive to save energy determines transcript quantities and their location while acting differently on each molecular species depending on the length, longevity and other features of the respective molecule. We combined our own data and experimental reports from five other large-scale mRNA and proteomics screens, comprising more than ten thousand molecular species to reveal the underlying computational principles of molecular localisation. We found that energy minimisation principles explain experimentally-reported exponential rank distributions of mRNA and protein copy numbers. Our results further reveal robust energy benefits when certain mRNA classes are moved into dendrites, for example mRNAs of proteins with long amino acid chains or mRNAs with large non-coding regions and long half-lives proving surprising insights at the level of molecular populations.