RNA Methylation in Plants and Man: The Catabolism of modified Nucleotides from RNA decay by N6-methy-AMP Aminohydrolase.

RNA post-transcriptional modification mostly by methylation is a newly emerging highly dynamic field of research. N⁶-methyladenosine (m⁶A) is the most abundant internal modification in messenger RNAs of eukaryotic species. It modulates mRNA characteristics influencing RNA processing, translation and RNA decay. So far, the fate of modified nucleotides after RNA degradation has not been elucidated for any altered nucleotide in any organism. We identified and partially characterized a novel enzyme, N⁶-methyl-AMP (N⁶-mAMP) aminohydrolase, which clears the methyl marker from N⁶-mAMP. Corresponding mutants accumulate N⁶-mAMP in vivo. This is the first enzyme discovered to be involved in the catabolism of modified nucleotides in any organism. We propose to further investigate the relationship of N⁶-mAMP catabolism and RNA m⁶A dynamics in plants and in human cells. We will extend our research towards establishing methods for the detection of other modified nucleotides derived from mRNA such as N¹-mAMP and pseudouridine and to elucidate their metabolic fate. We envisage that defective removal or end-storage of modified nucleotides may have profound effects on the homeostasis of RNA modification.

Project duration: 16 months