2014 Fiscal Year Final Research Report
Analysis of hepatic carcinogenesis by interrelationship between RNA-binding oncogene and miRNAs
| Project/Area Number |
24659362
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | RNA結合蛋白 / 肝癌 / mRNA processing / mRNA splicing / CLIP / spliceosome / BRCA1 / homologous recombination |
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| Outline of Final Research Achievements |
CIRP is one of RNA binding proteins, and induced by stress responces, which include moderate cold stress, ultraviolet, and hypoxia. CIRP functions as oncogene, because CIRP induces mouse primary cell immortalization and transformation. To identify CIRP protein-bound mRNA transcripts in whole transcriptome of human hepatoblastoma cell line HepG2, we apply crosslinking and immunoprecipitation(CLIP). CIRP binds mRNA transcripts of Mre11, Rad50, Rad52, NBS, and ATM, that are involved in DNA repair by BRCA1-associated homologous recombination after DNA damage. However, CIRP does not complex with transcripts of Ku80, XRCC4-like, and DNA-PK, that are involved in DNA repair by non-homologous end joining (NHEJ). Spliceosome contains CIRP. CIRP binds phospho-BRCA1 in the nucleus. phospho-BRCA1-CIRP complex undergoes efficient mRNA processing and splicing, and enhances expression of mature transcripts, facilitating resistance against DNA damage.
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| Free Research Field |
分子腫瘍学
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