Mutational Analysis Reveals Functional Roles of METTL16 Domains and Residues.

ABSTRACT: Human methyltransferase-like protein 16 (METTL16) installs N⁶-methyladenosine on U6 small nuclear RNA (snRNA) and other RNAs. Multiple X-ray crystal structures of METTL16 have been published; however, we do not yet fully understand the structure-function relationships of specific residues. We designed 38 mutants, including seven cancer-associated mutants, and used electrophoretic mobility shift assays and single-turnover kinetic assays to better understand the functional roles of specific domains and amino acid residues in binding to U6 snRNA, formation of the METTL16•U6 snRNA•S-adenosylmethionine (SAM) complex, and the rate of methylation. While point mutations in the methyltransferase domain mildly weaken the binding of METTL16 to U6 snRNA, the C-terminal vertebr

SUBMITTER: Breger K 

PROVIDER: S-EPMC12467241 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature