Regulation of erythroid differentiation by RNA methylation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15372
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Yoshinaga Masanori 京都大学, 医学研究科, 助教 (70878347)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: RNA修飾 / 赤芽球分化 / DNA損傷

Outline of Final Research Achievements

The purpose of this study was to elucidate the role of METTL16, an RNA methyltransferase, in erythropoiesis. Erythroblast-specific METTL16-deficient mice exhibit severe anemia, leading to embryonic lethality. We found that micronuclei, a marker of DNA damage, are frequently observed in METTL16-deficient erythroblasts. Furthermore, METTL16 enables erythroid differentiation by depositing RNA modifications to mRNAs encoding genes related to DNA repair and positively regulating the expression of these genes. These results suggest that RNA modifications mediated by METTL16 play an important role in the regulation of hematopoiesis in mammals.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

本研究により、METTL16を介したRNA修飾の造血とDNA修復における意義が明らかとなった。また、METTL16により修飾を受けるmRNAの包括的な理解につながった。本研究は新たな赤芽球分化制御機構としてのRNA修飾の役割の理解に寄与し、貧血をはじめとする赤血球造血異常の病態解明や新規治療法・治療薬の創出にも波及することが期待される。