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2023 Fiscal Year Final Research Report

Pathological significance of transcriptional activation of non-coding DNA by DUX4

Research Project

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Project/Area Number 21K07426
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionTokai University

Principal Investigator

Mitsuhashi Hiroaki  東海大学, 工学部, 准教授 (20466220)

Co-Investigator(Kenkyū-buntansha) 三橋 里美  聖マリアンナ医科大学, 医学部, 教授 (40466222)
中川 草  東海大学, 医学部, 准教授 (70510014)
Project Period (FY) 2021-04-01 – 2024-03-31
KeywordsDUX4 / FSHD / 非コードDNA / 筋ジストロフィー
Outline of Final Research Achievements

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant inherited muscle disease and is thought to be caused by the expression of the transcription factor DUX4-fl, which is not expressed in skeletal muscle of healthy individuals. In this study, we focused on the noncoding DNAs activated by DUX4-fl, and revealed the full length sequences of the noncoding DNAs using a long-read sequencer. Among them, we found several non-coding DNAs that may have been translated. Thus, we cloned ORFs of those noncoding DNAs, and overexpressed them in human-derived cultured cell lines. As the results, we confirmed that the proteins were translated from the non-coding DNA-derived ORFs. Further studies are needed to elucidate the relationship between the expression of these proteins and the pathogenesis of FSHD.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

顔面肩甲上腕型筋ジストロフィーの原因遺伝子DUX4-flの発現は様々な細胞障害を引き起こし、最終的に細胞死を起こすが、DUX4-flの下流で細胞障害の原因となる特定のタンパク質はまだ同定されていない。本研究ではDUX4-flの下流の非コードDNAを網羅的に探索し、その完全長を同定した。このデータをデータベースに公開することにより、今後、FSHDの病態解明に向けた研究を加速することに寄与できると考えている。また、本研究では非コードDNAと考えられてきた領域からの翻訳の可能性を示唆することができたため、非コードDNAの意義を再考するような学術的な意義を持つものと考えている。

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Published: 2025-01-30  

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