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m6A RNA Degradation Products Are Catabolized by an Evolutionarily Conserved N6-Methyl-AMP Deaminase in Plant and Mammalian Cells
- Source :
- The Plant Cell. 30:1511-1522
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
Abstract
- N(6)-methylated adenine (m(6)A) is the most frequent posttranscriptional modification in eukaryotic mRNA. Turnover of RNA generates N(6)-methylated AMP (N(6)-mAMP), which has an unclear metabolic fate. We show that Arabidopsis thaliana and human cells require an N(6)-mAMP deaminase (ADAL, renamed MAPDA) to catabolize N(6)-mAMP to inosine monophosphate in vivo by hydrolytically removing the aminomethyl group. A phylogenetic, structural, and biochemical analysis revealed that many fungi partially or fully lack MAPDA, which coincides with a minor role of N(6)A-RNA methylation in these organisms. MAPDA likely protects RNA from m(6)A misincorporation. This is required because eukaryotic RNA polymerase can use N(6)-mATP as a substrate. Upon abrogation of MAPDA, root growth is slightly reduced, and the N(6)-methyladenosine, N(6)-mAMP, and N(6)-mATP concentrations are increased in Arabidopsis. Although this will potentially lead to m(6)A misincorporation into RNA, we show that the frequency is too low to be reliably detected in vivo. Since N(6)-mAMP was severalfold more abundant than N(6)-mATP in MAPDA mutants, we speculate that additional molecular filters suppress the generation of N(6)-mATP. Enzyme kinetic data indicate that adenylate kinases represent such filters being highly selective for AMP versus N(6)-mAMP phosphorylation. We conclude that a multilayer molecular protection system is in place preventing N(6)-mAMP accumulation and salvage.
- Subjects :
- 0301 basic medicine
Inosine monophosphate
RNA Stability
Arabidopsis
Adenylate kinase
Plant Science
Biology
In Brief
AMP Deaminase
03 medical and health sciences
chemistry.chemical_compound
RNA polymerase
Animals
RNA, Messenger
Research Articles
Phylogeny
Messenger RNA
Arabidopsis Proteins
Kinase
fungi
Eukaryota
RNA
AMP deaminase
Cell Biology
biology.organism_classification
030104 developmental biology
Biochemistry
chemistry
Transcriptome
Subjects
Details
- ISSN :
- 1532298X and 10404651
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- The Plant Cell
- Accession number :
- edsair.doi.dedup.....6b69b33d9edc496b4d2a89023faa3b9f