Elucidation of inhibitory mechanism of binding of long noncoding RNA via arginine methylation and its physiological significance
| Project/Area Number |
18K06939
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Saitama Medical University |
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Principal Investigator |
KUROKAWA Riki 埼玉医科大学, 医学部, 教授 (70170107)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | アルギニンメチル化 / TLS / FUS / lncRNA / pncRNA-D / 相分離 / HAT / PRMT1 / RNA結合タンパク質 / RNA結合たんぱく質 / arginine / methylation / long noncoding RNA / histone acetylation |
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| Outline of Final Research Achievements |
Our previous data demonstrate that RNA-binding protein (RBP) TLS/FUS binds promoter-associated noncoding RNA-D (pncRNA-D) and strongly represses the CBP/p300 histone acetyltransferase (HAT) activity (Wang et al. Nature 2008). Recently, we have shown that protein arginine (R) methyltransferase 1(PRMT1)methylates arginine residues of the C-terminus of TLS and this R methylation represses RNA binding of TLS and also its inhibitory effect on the HAT activity. These data present a novel and comprehensive model showing that R methylation of TLS modulates its function and also regulates expression of relevant genes in the human genome.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで、TLS/FUSを含む多くのRNA結合タンパク質(RBP)が高度にアルギニン(R)メチル化されていることが知られていたが、その生理的な意義は大部分不明であった。今回の成果で、TLSのRメチル化が、RBPの中心的な機能であるRNA結合を制御することが明らかになった学術的な意義は大きい。今後は、この現象がほかのRBPでも機能していることをゲノムワイドで解明していきたい。一方、タンパク質のRメチル化は、大腸がんの発症や、胎生期の大脳の発達、iPS細胞の万能性の維持などに必須であり、これらの分子機構を解明することは社会的な要求に貢献することになろう。
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Report
(6 results)
Research Products
(13 results)
