Searching the mechanisms of mRNA buffering: the releasing-shuttling model

Many experiments showed that eukaryotic cells maintain a constant mRNA concentration upon various perturbations by actively regulating mRNA production and degradation rates, known as mRNA buffering. However, the underlying mechanism is still unknown. Here, we propose a mechanistic model of mRNA buffering: the releasing-shuttling (RS) model. The model incorporates two crucial factors, X and Y, which play key roles in the transcription, exportation, and degradation processes. The model explains the constant mRNA concentration under genome-wide genetic perturbations and cell volume changes. Moreover, it quantitatively explains the slowed-down mRNA degradation after Pol II depletion and the temporal transcription dynamics after Xrn1 depletion. The RS model suggests that X and Y are likely composed of multiple molecules possessing redundant functions. We also present a list of X and Y candidates, and an experimental method to identify X. Our work uncovers a possible coupling mechanism between transcription, exportation, and degradation.