Splice site m<sup>6</sup>A methylation prevents binding of U2AF35 to inhibit RNA splicing.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33930289.
- Also identified by DOI 10.1016/j.cell.2021.03.062 and PMC identifier 8208822.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) RNA modification is used widely to alter the fate of mRNAs. Here we demonstrate that the C. elegans writer METT-10 (the ortholog of mouse METTL16) deposits an m<sup>6</sup>A mark on the 3' splice site (AG) of the S-adenosylmethionine (SAM) synthetase pre-mRNA, which inhibits its proper splicing and protein production. The mechanism is triggered by a rich diet and acts as an m<sup>6</sup>A-mediated switch to stop SAM production and regulate its homeostasis. Although the mammalian SAM synthetase pre-mRNA is not regulated via this mechanism, we show that splicing inhibition by 3' splice site m<sup>6</sup>A is conserved in mammals. The modification functions by physically preventing the essential splicing factor U2AF35 from recognizing the 3' splice site. We propose that use of splice-site m<sup>6</sup>A is an ancient mechanism for splicing regulation.
Medical subject headings
- Adenosine
- RNA Splice Sites
- RNA Splicing
- Splicing Factor U2AF