2022 Fiscal Year Annual Research Report
| Project/Area Number |
22J13110
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokyo |
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Principal Investigator |
韓 佩恂 東京大学, 新領域創成科学研究科, 特別研究員(DC2)
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| Project Period (FY) |
2022-04-22 – 2024-03-31
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| Keywords | Ribosome / Translation |
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| Outline of Annual Research Achievements |
Translation is a dynamic process during gene expression. It is known that cells harness the specific features encoded in mRNA sequences to regulate gene expression at translation level. One specific case during translation is when an upstream translating ribosome collides into a downstream ribosome. However, how cells utilize ribosome collisions to regulate gene expression remains unclear. Specifically, it is unclear whether certain types of ribosome collisions are recognized as deleterious and are subsequently subjected to translational quality control mechanisms.
Therefore, in this project I aim to further dissect the features of ribosome collisions which are targets of ribosome-associated quality control.
To focus on collided ribosomes that were rescued by quality control mechanism, key factors of ribosome-associated quality control were knocked down. Extensive analysis of deep-sequencing data provided evidence of endogenous features that contributed to ribosome collisions which were normally rescued by ribosome-associated quality control. Further validation of analysis results is currently undergoing to provide insights on the exact mechanism.
This project is expected to uncover the endogenous features of ribosome collisions that could be recognized by ribosome-associated quality control to further explain the role of ribosome collisions during translation.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Analysis of deep sequencing data was carried out as initially planned. From the analysis, preliminary evidence regarding features that contributed to ribosome collisions, which were normally rescued by quality control mechanism, were determined. Moreover, the findings were further examined using previously published data sets to provide insights into the possible mechanism that was involved. Through these results, it was possible to determine a working model regarding collided ribosomes which were targets of ribosome-associated quality control under native state.
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| Strategy for Future Research Activity |
Currently, further validation of analysis results is undergoing to provide evidence on the exact mechanism regarding the recognition of ribosome collisions by ribosome-associated quality control pathway.
To test the features of ribosome collisions that were rescued by ribosome quality control mechanism, I plan to utilize reporter assays in cell-free and cell-based conditions. By insertion of test features into reporter systems, it is possible to determine whether the feature is sensitive to the change in level of ribosome-associated quality control mechanism, specifically the changes of certain key factors. Moreover, using the reporter system, it is also possible to evaluate the impact that ribosome collisions have on translation process.
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