| Project/Area Number |
22700863
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Carcinogenesis
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
NAKANO Kazumi 東京大学, 大学院・新領域創成科学研究科, 助教 (60549591)
|
|---|
| Project Period (FY) |
2010 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | がん遺伝子 / ヒト白血病ウィルス / HTLV-1 / ATL / NMD / ウイルス自己複製 / ウイルスゲノムRNA |
|---|
| Research Abstract |
In the present study, we demonstrated that HTLV-1 infection induces the suppression of the host NMD activity, and that HTLV-1 Rex, the viral post-transcriptional regulator, is responsible for the NMD inhibition. Overexpression of Rex resulted in decreased NMD activity and increased stability of the viral genomic RNA. Moreover, Rex stabilized a native NMD target mRNA, such as nik mRNA. These results suggest that NMD inhibition by Rex is beneficial for the viral replication, but also can influence on the expression levels of aberrant mRNAs as well as native mRNAs targeted by NMD. We demonstrated that HTLV-1 infected T-cell lines have lower NMD activities than HTLV-1 uninfected T-cell lines. Also, gene expression microarray analyses showed that PBMCs from ATL patients have elevated NMD target mRNAs compared with those from healthy donors. Taken together, these results proposed a possibility that NMD disruption by Rex at the time of HTLV-1 infection may implicate in the immortalization and transformation of infected cells.
|
