Regulation of RNA-binding proteins affinity to export receptors enables the nuclear basket proteins to distinguish and retain aberrant mRNAs.
Export of messenger ribonucleic acids (mRNAs) into the cytoplasm is a fundamental step in gene regulation processes, which is meticulously quality controlled by highly efficient mechanisms in eukaryotic cells. Yet, it remains unclear how the aberrant mRNAs are recognized and retained inside the nucleus. Using a new modelling approach for complex systems, namely the agent-based modelling (ABM) approach, we develop a minimal model of the mRNA quality control (QC) mechanism. Our results demonstrate that regulation of the affinity of RNA-binding proteins (RBPs) to export receptors along with the weak interaction between the nuclear basket protein (Mlp1 or Tpr) and RBPs are the minimum requirements to distinguish and retain aberrant mRNAs. Our results show that the affinity between Tpr and RBPs is optimized to maximize the retention of aberrant mRNAs. In addition, we demonstrate how the length of mRNA affects the QC process. Since longer mRNAs spend more time in the nuclear basket to form a compact conformation and initiate their export, nuclear basket proteins could more easily capture and retain them inside the nucleus.
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, CA, 94720, USA.|Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, CA, 94720, USA.
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Soheilypour
Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, CA, 94720, USA.|Molecular Biophysics and Integrative Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
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Mofrad
D002467:Cell Nucleus / Q000378:metabolism; D003198:Computer Simulation; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D008962:Models, Theoretical; D009685:Nuclear Envelope / Q000378:metabolism; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D011786:Quality Control; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism*; D013597:Systems Analysis
D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins