| Project/Area Number |
18K19289
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
|
|---|
| Research Institution | Japan Advanced Institute of Science and Technology |
|---|
Principal Investigator |
Sakari Matomo 北陸先端科学技術大学院大学, 先端科学技術研究科, 研究員 (90466772)
|
|---|
| Project Period (FY) |
2018-06-29 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
|---|
| Keywords | m6A / エピトランスクリプトーム / RNA編集 / RNAメチル化 |
|---|
| Outline of Final Research Achievements |
The purpose of this study is to develop a technique for editing m6A modification of specific mRNA, and to analyze the function of m6A and to develop an RNA editing method for m6A modification abnormal diseases. As a development of RNA methylation editing platform, we have succeeded in demethylation editing of about 80%. As a new evaluation system, we developed a highly sensitive methylation evaluation method using MazF, a methylated RNA-sensitive RNase. It has become possible to calculate the editing efficiency with higher accuracy compared to the conventional IP method using an antibody. The effectiveness of the new methylated RNA editing platform was demonstrated by the development of these RNA editing systems and their evaluation methods, and showed the usefulness of the artificial RNA modification editing method.
|
| Academic Significance and Societal Importance of the Research Achievements |
RNAの多様な化学修飾によるRNAエピジェネティクスの全体像はその大部分が未解明であるものの、近年アデノシンのRNAメチル化酵素複合体としてMETTL3, METTL14, WTAPタンパク質群が見いだされ、またRNA脱メチル化酵素としてALKBH5が同定された。これらの遺伝子群のノックアウトマウスの表現型解析により、癌、糖尿病、肥満、生殖不全やアルコール依存症といった疾患との関連が示唆されている。しかしながら原因となる標的メチル化RNAの直接的な解析手法が少ない。本研究で開発されたRNAメチル化編集法によりm6A修飾の新たな解析法の提示が可能であると考える。
|
