Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.7.6 (
RNA polymerase
)
34,946
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:m
6
A RNA Degradation Products Are Catabolized by an Evolutionarily Conserved N
6
-Methyl-AMP Deaminase in Plant and Mammalian Cells. 2990 27
