2013 Fiscal Year Final Research Report
Dissection of mRNA degradation pathways and anomalies associated with targeted disruption of CCR4-NOT deadenylase complex
| Project/Area Number |
21229006
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Okinawa Institute of Science and Technology Graduate University (2011-2013)
The University of Tokyo (2009-2010) |
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Principal Investigator |
YAMAMOTO TADASHI 沖縄科学技術大学院大学, 細胞シグナルユニット, 教授 (40134621)
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| Project Period (FY) |
2009-05-11 – 2014-03-31
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| Keywords | mRNA代謝 / mRNA分解 / 遺伝子欠損マウス / 疾患モデル / CCR4-NOT複合体 / 脱アデニル化反応 / 3’UTR / poly(A)配列 |
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| Research Abstract |
We have studied the physiological roles of the CCR4-NOT deadenylase complex by generating mouse lines in which each gene encoding individual subunit of the CCR4-NOT complex is disrupted. Mice thus produced were analyzed pathologically and anatomically, and we so far found that those mice were either embryonic lethal or abnormal in tissue development or showed loss of regulation in immune system and/or energy metabolism. We, therefore, assumed that CCR4-NOT deficient mouse lines could be models of human diseases. We also analyzed the molecular mechanisms by which the CCR4-NOT complex recognizes and degrades poly(A) tail of its target mRNAs. We solved the crystal structures of oligo(dA)-interacting enzymatic subunits CNOT6L and CNOT7. We also found the enzymatic subunits can target poly(A) tail of specific mRNA species through their interaction with regulatory subunits such as CNOT1 and CNOT3 that can recognize specific sequences present at 3'UTR regions of particular mRNAs.
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Research Products
(51 results)
