Journal
CELL REPORTS
Volume 26, Issue 13, Pages 3762-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.02.100
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Funding
- Chemestmed Ltd.
- Centre of Excellence in Molecular Cell Engineering, Estonia [2014-2020.4.01.15-013]
- Estonian Research Council [PUT582]
- Finnish Foundation for Cardiovascular Research (Syda ntutkimussaatio)
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Chemical modifications of RNA provide an additional, epitranscriptomic, level of control over cellular functions. N-6-methylated adenosines (m6As) are found in several types of RNA, and their amounts are regulated by methyltransferases and demethylases. One of the most important enzymes catalyzing generation of m6A on mRNA is the trimer N-6-methyltransferase METTL3-14-WTAP complex. Its activity has been linked to such critical biological processes as cell differentiation, proliferation, and death. We used in silico-based discovery to identify small-molecule ligands that bind to METTL3-14-WTAP and determined experimentally their binding affinity and kinetics, as well as their effect on enzymatic function. We show that these ligands serve as activators of the METTL3-14-WTAP complex.
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