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Translatome Analysis Of Mitotic Arrested Cells And The Investigation Of Cell Fate Control

Posted on:2015-10-09Degree:MasterType:Thesis
Country:ChinaCandidate:X XuFull Text:PDF
GTID:2180330434466056Subject:Cell biology
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Recently, cancer has been one of the most threatening disease to human’s life and health. Anti-motosis chemotherapeutic drugs can affect the normal function of spindle and induce mitotic arrest. Based on the principle that arrested cells would die in mitosis, these drugs are being used to treat cancer. Besides mitotic cell death, however, arrested cells need to confront other fates. Thus, figuring out the machanism of cell fate control after mitotic arrest will do favor for efficacy improvement of anti-mitotic drugs. Scientific researchs related to cell fate control always focus on protein modification and degradation. There is no report on the new protein synthesis level.This research studied the translatome of mitotic and arrested cells by using ribosome profiling technology which has been well developed recent years. By bio-informatics analysis, we grouped the genes that had high translational level between these two groups according to their function. And we also studied the variation on single gene level, then validated the variation of several genes that have different translation by using molecular and cellular methods. Finally, we explored the influence of Notch2to the cell fate after mitotic arrest.After experiments, we got the information of all the translating mRNAs in mitotic and arrested cells. This information can reflect the synthesis of new proteins. Bio-informatics analysis indicate that, genes that under high translational level in mitotic and arrested cells belong to some certain functions. Most of them are the same in the two samples. But in arrested cells, some genes belong to two functions extracellular matrix-interation and leucocyte transendothelial migration--are still have high level of translation.This result indicate that these two functions may involved in cell fate control after mitotic arrest. Single gene translational variation analysis got103genes that have different translation. And the picked genes--Nothc2and MIF--exactly showed different translation. After Notch2downregulated, arrested cells prone to finish mitosis abnormally then dying in next G1phase. These data shows that the translational variation exactly exist in mitotic arrested cells. And these variation seems to related to cell fate control after mitotic arrest. Detailed machenism still needs intensive study.The paper was first analysed mitotic arrested cells on translational level. And studied the relationship between proteins that showed different transltion and the cell fate control after mitotic arrest. We hope that the results of this paper would shed a new light on further exploring the machenism of the cell fate control after mitotic arrest.
Keywords/Search Tags:mitotic arrest, cell fate control, Ribosome profiling, different translation, Notch2
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