SAM homeostasis is regulated by CFIm- mediated splicing of MAT2A

Anna M. Scarborough, Juliana N. Flaherty, Olga V. Hunter, Kuanqing Liu, Ashwani Kumar, Chao Xing, Benjamin P. Tu, Nicholas K. Conrad

Research output: Contribution to journalArticlepeer-review

Abstract

S-adenosylmethionine (SAM) is the methyl donor for nearly all cellular methylation events. Cells regulate intracellular SAM levels through intron detention of MAT2A, the only SAM synthetase expressed in most cells. The N6-adenosine methyltransferase METTL16 promotes splicing of the MAT2A detained intron by an unknown mechanism. Using an unbiased CRISPR knock-out screen, we identified CFIm25 (NUDT21) as a regulator of MAT2A intron detention and intracellular SAM levels. CFIm25 is a component of the cleavage factor Im (CFIm) complex that regulates poly(A) site selection, but we show it promotes MAT2A splicing independent of poly(A) site selection. CFIm25-mediated MAT2A splicing induction requires the RS domains of its binding partners, CFIm68 and CFIm59 as well as binding sites in the detained intron and 3' UTR. These studies uncover mechanisms that regulate MAT2A intron detention and reveal a previously undescribed role for CFIm in splicing and SAM metabolism.

Original languageEnglish (US)
Article numbere64930
JournaleLife
Volume10
DOIs
StatePublished - May 2021

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint

Dive into the research topics of 'SAM homeostasis is regulated by CFI<sub>m</sub>- mediated splicing of MAT2A'. Together they form a unique fingerprint.

Cite this