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Doctoral thesis
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The Conserved Role of METTL16 m6A Methyltransferase in Gene Expression Regulation

ContributorsMendel, Mateusz
Number of pages178
Imprimatur date2021-09-05
Defense date2021-09-01
Abstract

RNA modifications emerged recently as a new layer of post-transcriptional gene expression regulation. The most common internal messenger RNA (mRNA) modification is N6-methyladenosine (m6A). It is deposited on pre-mRNA by two methyltransferases: METTL3-METTL14 heterodimer and METTL16. METTL3/14 deposits most m6A in the cell and is essential for embryonic development in plants and animals. The role of METTL16 methyltransferase is much less understood. My research aimed to understand the role of METTL16 in gene expression regulation in mice and C. elegans. In this thesis, I show that METTL16 controls S-adenosylmethionine (SAM) synthetase pre-mRNA splicing both in mice and C. elegans and is essential for SAM levels regulation. In C. elegans, SAM synthetase pre-mRNA splicing is inhibited by deposition of m6A at the 3′ splice site (3'SS), preventing an essential splicing factor U2AF35 binding. Although SAM synthetase splicing is regulated differently in mammals, the mechanism of splicing inhibition by 3′SS m6A methylation is conserved. Thus, I propose that splice-site m6A is an ancient mechanism for splicing regulation.

eng
Keywords
  • METTL16
  • METT-10
  • U2AF35
  • RNA modifications
  • N6-methyladenosine
  • RNA splicing
Research group
Citation (ISO format)
MENDEL, Mateusz. The Conserved Role of METTL16 m6A Methyltransferase in Gene Expression Regulation. 2021. doi: 10.13097/archive-ouverte/unige:159126
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Creation02/21/2022 12:01:00 AM
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