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Human METTL16 is a N 6 ‐methyladenosine (m 6 A) methyltransferase that targets pre‐mRNAs and various non‐coding RNAs
Author(s) -
Warda Ahmed S,
Kretschmer Jens,
Hackert Philipp,
Lenz Christof,
Urlaub Henning,
Höbartner Claudia,
Sloan Katherine E,
Bohnsack Markus T
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744940
Subject(s) - methyltransferase , rna , biology , chemistry , microbiology and biotechnology , physics , genetics , methylation , gene
N 6 ‐methyladenosine (m 6 A) is a highly dynamic RNA modification that has recently emerged as a key regulator of gene expression. While many m 6 A modifications are installed by the METTL 3– METTL 14 complex, others appear to be introduced independently, implying that additional human m 6 A methyltransferases remain to be identified. Using crosslinking and analysis of cDNA ( CRAC ), we reveal that the putative human m 6 A “writer” protein METTL 16 binds to the U6 sn RNA and other nc RNA s as well as numerous lnc RNA s and pre‐ mRNA s. We demonstrate that METTL 16 is responsible for N 6 ‐methylation of A43 of the U6 sn RNA and identify the early U6 biogenesis factors La, LARP 7 and the methylphosphate capping enzyme MEPCE as METTL 16 interaction partners. Interestingly, A43 lies within an essential ACAGAGA box of U6 that base pairs with 5′ splice sites of pre‐ mRNA s during splicing, suggesting that METTL 16‐mediated modification of this site plays an important role in splicing regulation. The identification of METTL 16 as an active m 6 A methyltransferase in human cells expands our understanding of the mechanisms by which the m 6 A landscape is installed on cellular RNAs.