Elucidation of crosstalk in miRNA-lncRNA-mRNA network on pathophysiological events

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Kochi University
• Principal Investigator: Sakamoto Shuji 高知大学, 教育研究部医療学系基礎医学部門, 教授 (80397546)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: RNA結合タンパク質 / 骨格筋萎縮 / 非翻訳RNA / 細胞融合 / NF90 / NF45 / Myomaker/Myomixer

Outline of Final Research Achievements

We previously found that overexpression of NF90-NF45 complex, a RNA-binding protein, induces skeletal muscle atrophy. This study demonstrated that the muscle atrophy is deeply correlated with constitutive expression of Myomaker (MYMK)/Myomixer (MYMX) which are responsible factors for myoblast fusion during myogenesis. It is known that the expression of MYMK/MYMX is controlled by MyoD and MyoG which are myogenic regulatory factors. Finally, we newly found that the constitutive expression of MYMK/MYMX is caused by coordination via NF90-NF45 between “a network of lncRNA(pri-miR-378a) accumulation-miRNA(miR-378a-3p) reduction-mRNA(MyoG mRNA) increment” and “an activation of transcriptional ability of MyoD”, resulting in the skeletal muscle atrophy.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

NF90-NF45の発現上昇による骨格筋萎縮は筋繊維の中心に核が局在する「中心核化」を呈する。この「中心核化」は、筋力低下等の病態を呈する「筋強直性ジストロフィー I型(DM1)」や「中心核病」等でも確認される。近年、DM1の生検においてNF90-NF45の発現上昇が確認されている(Sabater-Arcis et al. Mol. Ther. Nucleic Acids 2020)。従って、本研究で見出された「NF90-NF45の高発現による中心核化を伴う筋萎縮の新規分子メカニズム」は、筋疾患DM1及び中心核病の発症機序解明や治療薬開発等において有益な情報になり得るものと考えている。