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Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases
Open accessAbstract
Summary N6-methyladenosine (m6A) is a prevalent, reversible chemical modification of functional RNAs, and is important for central events in biology. The core m6A writers are Mettl3 and Mettl14, which both contain methyltransferase domains. How Mettl3 and Mettl14 cooperate to catalyze methylation of adenosines has remained elusive. We present crystal structures of the complex of Mettl3/Mettl14 methyltransferase domains in apo form as well as with bound S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) in the catalytic site. We determine that the heterodimeric complex of methyltransferase domains, combined with CCCH motifs constitute the minimally required regions for creating m6A modifications in vitro. We also show that Mettl3 is the catalytically active subunit while Mettl14 plays a structural role critical for substrate recognition. Our model provides a molecular explanation for why certain mutations of Mettl3 and Mettl14 lead to impaired function of the methyltransferase complex.
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“Methylation of adenosine in mRNAs is catalyzed by a methyltransferase complex containing METTL3 (also called MT-A70, MTA and IME4) in cooperation with METTL14.”
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Metadata
- Authors
- Wang, P., Doxtader, K. A., & Nam, Y.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 63
- Issue
- 2
- Pages
- 306-317
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2472887612
- Cited by
- 1,246
- References
- 8
- FWCI
- 27.84
- Type
- journal article
- Language
- en
- Open access
- bronze
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