Item type:Thesis, Open Access

Characterisation of the role of Mettl3-mediated m6A methylation in skeletal muscle cells

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2026-01-12

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Philipps-Universität Marburg
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Abstract

A growing body of evidence suggests a pivotal role of N6-Methyladenosine (m6A) modifications for biological processes, including stem cell differentiation. While initial steps have been taken to explore the influence of m6A on muscle stem cell (MuSC) development, several open questions remain, including contradictory findings about the regulation of MuSCs by m6A. These include dual effects of METTL3 on proliferation and differentiation, identification of direct m6A targets, underlying mechanisms, and the roles of (non-)canonical m6A binding proteins. My research focused on the function of Mettl3-mediated m6A modifications for skeletal muscle cell development and regeneration, revealing effects of m6A on proliferation and differentiation of MuSCs. My study revealed the requirement of Mettl3 in Pax7- positive MuSCs for efficient muscle cell differentiation. Furthermore, several potential direct m6A targets were identified, including COUP-TFII (Nr2f2), a transcription factor involved in the pathogenesis of Duchenne muscular dystrophy. My investigations highlight the role of m6A in the metabolism of Ribonucleic acids (RNAs), particularly RNA stability and translation. It demonstrates that Mettl3 strongly influences mRNA degradation and splicing, disclosing that genes differentially expressed in m6A-deficient MuSCs often show changes in the splicing patterns. The study also examines m6A proteins that interact with m6A-modified RNAs and demonstrates the existence of non-canonical m6A readers. Novel methodologies such as GLORI-Sequencing were established and applied to muscle cells for improving detection of m6A and enabling stoichiometric identification of m6A sites at single nucleotide resolution. Complex m6A methylation patterns were mapped, and their interplay with RNA G-quadruplexes (RG4s) were explored, suggesting links between RG4s and epitranscriptomic changes. In conclusion, my research answers several questions about the function of m6A- dependent processes in muscle stem cell development. The identification of direct targets, mechanisms, and interactions improves understanding of the role of epitranscriptomics for critical cellular activities

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Dates
Created: 2025Issued: 2026-01-12Updated: 2025-07-09
DOI
https://doi.org/10.17192/z2025.0496
Faculty
Fachbereich Biologie
Publisher
Philipps-Universität Marburg
Language
eng
Data types
DoctoralThesis
DDC-Numbers
570
License
https://creativecommons.org/licenses/by-nc-nd/4.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2025.0496
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Law, Justin Yiu Chun: Characterisation of the role of Mettl3-mediated m6A methylation in skeletal muscle cells. : Philipps-Universität Marburg 2026-01-12. DOI: https://doi.org/10.17192/z2025.0496.

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Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 - CC BY NC ND
Except where otherwised noted, this item's license is described as Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 - CC BY NC ND