◆Research findings by Assistant Professor Takuma Higuchi and Professor Shuichi Sakamoto of the Department of Basic Medical Sciences, Division of Education and Research ( Medical School) have been published in “FEBS Open Bio,” the academic journal of the Federation of European Biochemical Societies (FEBS).
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Researchers Discover Regulatory Mechanism of "RNA Modification" That Influences the Production of MicroRNAs Involved in Cancer Development
Research findings by Assistant Professor Takuma Higuchi and Professor Shuichi Sakamoto of the Department of Basic Medical Sciences Medical Schoolwere published in the academic journal *FEBS Open Bio*, published by the Federation of European Biochemical Societies, and the online version was released on December 6, Reiwa 7.
MicroRNAs (miRNAs) are functional small RNA molecules; since their expression levels fluctuate in various diseases, including cancer, they are expected to be utilized as disease markers and therapeutic targets.In recent years, it has been reported that methylation ( m6A modification ) of the adenine base in miRNA precursor transcripts (pri-miRNAs) leads to the promotion of miRNA biosynthesis. The m6A modification of pri-miRNAs is carried out by the methyltransferase complex METTL3/14.However, many aspects of the regulatory mechanism governing m6A modification of pri-miRNAs by METTL3/14 remain unclear.
Our research group has previously discovered that the complex of Nuclear Factor 90 (NF90), a double-stranded RNA-binding protein, and its binding partner NF45 (NF90–NF45) binds to pri-miRNAs and negatively regulates miRNA biogenesis.In this study, we demonstrated that NF90–NF45 inhibits m6A modification of pri-miRNAs that exhibit high binding affinity for the complex.
In this study, we focused specifically on the primary transcripts (pri-mir-7-1 and pri-mir-186) of the tumor-suppressor miRNAs “miR-7” and “miR-186,” which exhibit high binding affinity for NF90–NF45, and conducted an analysis.The results demonstrated that pri-mir-7-1 and pri-mir-186 undergo m6A modification by METTL3/14, and that NF90–NF45 significantly inhibits this m6A modification.In contrast, no inhibitory effect of NF90–NF45 on m6A modification was observed for pri-mir-200a, which has low binding affinity for NF90–NF45. Based on these findings, a molecular mechanism model was proposed: “NF90–NF45 binds to pri-miRNAs, thereby blocking METTL3/14 access to them and, as a result, inhibiting m6A modification.”
Overexpression of NF90–NF45 has been reported in various tissue-derived cancers, and these research findings are expected to contribute to elucidating the mechanisms underlying miRNA expression changes associated with cancer development.
<論文情報>
タイトル: Domain associated with zinc fingers-containing NF90-NF45 complex inhibits m6A modification of primary microRNA by suppressing METTL3/14 activity
著者: Takuma Higuchi, Shunsuke Morioka, Keiko Morisawa, Kazutsugu Matsukawa, Shingo Ashida, Takeshi Suzuki, Shuji Sakamoto
掲載誌: FEBS Open Bio
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