Genetic Interaction of tRNA-Dependent Mistranslation with Fused in Sarcoma Protein Aggregates
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plasmids and Strains
2.2. Cell Culture and Transfections
2.3. tRNA Sequencing
2.4. Fluorescence Microscopy
2.5. Semi-Denaturing Detergent Agarose Gel Electrophoresis (SDD-AGE)
3. Results
3.1. Protein Production in Mistranslating Cells
3.2. tRNA Sequencing Identifies and Quantitates tRNASerAAA Abundance in Mistranslating Cells
3.3. Aggregation of FUS Alleles in Normal and Mistranslating Cells
3.4. Toxicity of FUS Alleles in Mistranslating Cells
3.5. Kinetics of FUS Protein Production in Normal and Mistranslating Cells
3.6. FUS Aggregation Kinetics in Normal and Mistranslating Cells
3.7. FUS R521C Aggregation Kinetics in Normal and Mistranslating Cells
3.8. Measuring Total FUS Aggregate Levels in Normal and Mistranslating Cells
4. Discussion
4.1. De-Regulated Protein Homeostasis in ALS and in Cells Expressing Mutant or Wild-Type tRNAs
4.2. Considerations of Transfer RNA Variants as Therapeutics
4.3. Transfer RNA Variants as Modifiers of Neurodegenerative Diseases
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Lant, J.T.; Hasan, F.; Briggs, J.; Heinemann, I.U.; O’Donoghue, P. Genetic Interaction of tRNA-Dependent Mistranslation with Fused in Sarcoma Protein Aggregates. Genes 2023, 14, 518. https://doi.org/10.3390/genes14020518
Lant JT, Hasan F, Briggs J, Heinemann IU, O’Donoghue P. Genetic Interaction of tRNA-Dependent Mistranslation with Fused in Sarcoma Protein Aggregates. Genes. 2023; 14(2):518. https://doi.org/10.3390/genes14020518
Chicago/Turabian StyleLant, Jeremy T., Farah Hasan, Julia Briggs, Ilka U. Heinemann, and Patrick O’Donoghue. 2023. "Genetic Interaction of tRNA-Dependent Mistranslation with Fused in Sarcoma Protein Aggregates" Genes 14, no. 2: 518. https://doi.org/10.3390/genes14020518
APA StyleLant, J. T., Hasan, F., Briggs, J., Heinemann, I. U., & O’Donoghue, P. (2023). Genetic Interaction of tRNA-Dependent Mistranslation with Fused in Sarcoma Protein Aggregates. Genes, 14(2), 518. https://doi.org/10.3390/genes14020518