Posttranscriptional regulation of iron metabolism via RNA methylation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22737
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: Kyoto University
• Principal Investigator: Yoshinaga Masanori 京都大学, 医学研究科, 助教 (70878347)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: RNA修飾 / 鉄代謝 / 赤芽球分化

Outline of Final Research Achievements

In this study, we investigated the roles of a novel RNA m6A methyltransferase METTL16 in the regulation of iron metabolism. We revealed that the mice that lack METTL16 specifically in erythroblasts lead to embryonic death due to severe anemia. Moreover, METTL16-deficient erythroblasts failed to express erythroid transcription factors GATA-1 and KLF1, and iron-related genes including transferrin receptor. Next, we investigated the molecular mechanisms that act downstream of METTL16 and revealed that MTR4-nuclear exosome is critically involved in the mRNA regulation mediated by METTL16. These findings establish the novel mechanisms of gene expression of iron-regulatory transcripts mediated by METTL16.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

本研究により、これまで不明であったMETTL16の生体における機能の一端が解明された。また、METTL16の下流で作用する分子機構を網羅的に探索し、はじめてm6A修飾とMTR4-核内エクソソームの関係性を明らかにした。本研究成果は貧血をはじめとする鉄代謝異常や造血器疾患の病態の理解に寄与すると考えられる。