| Project/Area Number |
26840043
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
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| Research Institution | The University of Tokyo (2015)
National Institute of Advanced Industrial Science and Technology (2014) |
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Principal Investigator |
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| Research Collaborator |
TOMITA Kozo
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ガン / マイクロRNA / ウリジル化 / 酸化ストレス / ポリADPリボース / 癌化 / ポリウリジル化 |
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| Outline of Final Research Achievements |
let-7 miRNA functions as a tumor suppressor through oncogene repression. precursor let-7 (pre-let-7) is known to be polyuridylated at its 3' terminus by poly(U) polymerase TUT4/TUT7 in cancer cell lines. Polyuridylated pre-let-7 is a poor substrate for Dicer and rapidly degraded by exonuclease Dis3l2. Thus, polyuridylation of pre-let-7 results in decreased expression of mature let-7 and contributes to tumorigenesis.
In our current study, PARP13, one of human PARP homologues, was identified as a new intereactor for TUT7. This suggests that TUT4/7 could be modified and regulated by PAR. In fact, we found that PAR was associated with TUT4/7 and diminished pre-let-7 polyuridylation in vitro and in vivo. we also found oxidative stress leads to the increased amount of PAR associated with TUT4/7, while pre-let-7 polyuridylaiton was severely inhibited. This is a new example of expanding roles of PAR in post-transcriptional gene regulation and provides insight into cellular stress response.
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