Circadian rhythm shows potential for mRNA efficiency and self-organized division of labor in multinucleate cells

Abstract

AbstractMultinucleate cells occur in every biosphere and across the kingdoms of life, including in the human body as muscle cells and bone-forming cells. Data from filamentous fungi suggest that, even when bathed in a common cytoplasm, nuclei are capable of autonomous behaviors, including division. How does this potential for autonomy affect the organization of cellular processes between nuclei? Here we analyze a simplified model of circadian rhythm, a form of cellular oscillator, in a mathematical model of the filamentous fungus Neurospora crassa. Our results highlight the role played by mRNA-protein phase separation to keep mRNAs close to the nuclei from which they originate, while allowing proteins to diffuse freely between nuclei. Our modeling shows that syncytism allows for extreme mRNA efficiency — we demonstrate assembly of a robust oscillator with transcription levels 104-fold less than in comparable uninucleate cells. We also show self-organized division of the labor of mRNA production, with one nucleus in a two-nucleus syncytium producing at least twice as many mRNAs as the other in 30% of cycles. This division can occur spontaneously, but division of labor can also be controlled by regulating the amount of cytoplasmic volume available to each nucleus. Taken together, our results show the intriguing richness and potential for emergent organization among nuclei in multinucleate cells. They also highlight the role of previously studied mechanisms of cellular organization, including nuclear space control and localization of mRNAs through RNA-protein phase separation, in regulating nuclear coordination.Author summaryCircadian rhythms are among the most researched cellular processes, but limited work has been done on how these rhythms are coordinated between nuclei in multinucleate cells. In this work, we analyze a mathematical model for circadian oscillations in a multinucleate cell, motivated by frequency mRNA and protein data from the filamentous fungus Neurospora crassa. Our results illuminate the importance of mRNA-protein phase separation, in which mRNAs are kept close to the nucleus in which they were transcribed, while proteins can diffuse freely across the cell. We demonstrate that this phase separation allows for a robust oscillator to be assembled with very low mRNA counts. We also investigate how the labor of transcribing mRNAs is divided between nuclei, both when nuclei are evenly spaced across the cell and when they are not. Division of this labor can be regulated by controlling the amount of cytoplasmic volume available to each nucleus. Our results show that there is potential for emergent organization and extreme mRNA efficiency in multinucleate cells.