Abstract:
:N6-methyladenosine (m6A) is a highly dynamic RNA modification that has recently emerged as a key regulator of gene expression. While many m6A modifications are installed by the METTL3-METTL14 complex, others appear to be introduced independently, implying that additional human m6A methyltransferases remain to be identified. Using crosslinking and analysis of cDNA (CRAC), we reveal that the putative human m6A "writer" protein METTL16 binds to the U6 snRNA and other ncRNAs as well as numerous lncRNAs and pre-mRNAs. We demonstrate that METTL16 is responsible for N6-methylation of A43 of the U6 snRNA and identify the early U6 biogenesis factors La, LARP7 and the methylphosphate capping enzyme MEPCE as METTL16 interaction partners. Interestingly, A43 lies within an essential ACAGAGA box of U6 that base pairs with 5' splice sites of pre-mRNAs during splicing, suggesting that METTL16-mediated modification of this site plays an important role in splicing regulation. The identification of METTL16 as an active m6A methyltransferase in human cells expands our understanding of the mechanisms by which the m6A landscape is installed on cellular RNAs.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Warda AS,Kretschmer J,Hackert P,Lenz C,Urlaub H,Höbartner C,Sloan KE,Bohnsack MTdoi
10.15252/embr.201744940subject
Has Abstractpub_date
2017-11-01 00:00:00pages
2004-2014issue
11eissn
1469-221Xissn
1469-3178pii
embr.201744940journal_volume
18pub_type
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