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Structural insights into the RNA methyltransferase domain of METTL16.

Structural insights into the RNA methyltransferase domain of METTL16.
Author Information (click to view)

Ruszkowska A, Ruszkowski M, Dauter Z, Brown JA,


Ruszkowska A, Ruszkowski M, Dauter Z, Brown JA, (click to view)

Ruszkowska A, Ruszkowski M, Dauter Z, Brown JA,

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Scientific reports 2018 03 288(1) 5311 doi 10.1038/s41598-018-23608-8

Abstract

N-methyladenosine (mA) is an abundant modification in messenger RNA and noncoding RNAs that affects RNA metabolism. Methyltransferase-like protein 16 (METTL16) is a recently confirmed mA RNA methyltransferase that methylates U6 spliceosomal RNA and interacts with the 3′-terminal RNA triple helix of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1). Here, we present two X-ray crystal structures of the N-terminal methyltransferase domain (residues 1-291) of human METTL16 (METTL16_291): an apo structure at 1.9 Å resolution and a post-catalytic S-adenosylhomocysteine-bound complex at 2.1 Å resolution. The structures revealed a highly conserved Rossmann fold that is characteristic of Class I S-adenosylmethionine-dependent methyltransferases and a large, positively charged groove. This groove likely represents the RNA-binding site and it includes structural elements unique to METTL16. In-depth analysis of the active site led to a model of the methyl transfer reaction catalyzed by METTL16. In contrast to the major mA methyltransferase heterodimer METTL3/METTL14, full-length METTL16 forms a homodimer and METTL16_291 exists as a monomer based on size-exclusion chromatography. A native gel-shift assay shows that METTL16 binds to the MALAT1 RNA triple helix, but monomeric METTL16_291 does not. Our results provide insights into the molecular structure of METTL16, which is distinct from METTL3/METTL14.

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