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 transcription and degradation rates, known as mRNA buffering. However, the mechanism of mRNA buffering is still unknown. In this study, we propose a mechanistic model of mRNA buffering called the releasing-shuttling (RS) model. The model incorporates two crucial factors, X and Y, which play significant roles in the transcription, exportation, and degradation processes. The model successfully explains the constant mRNA concentration under genome-wide genetic perturbations and 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 potential X and Y candidates and an experimental method to identify X. Our work sheds light on a novel coupling mechanism between mRNA transcription, exportation, and degradation.