tRNA (adenine(58)-N(1))-methyltransferase catalytic subunit TRMT61A
mRNA (adenine-N1-)-methyltransferase activity
Base-Resolution Mapping Reveals Distinct m<sup>1</sup>A Methylome in Nuclear- and Mitochondrial-Encoded Transcripts.
Gene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N<sup>1</sup>-methyladenosine (m<sup>1</sup>A) is a recently identified mRNA modification; however, little is known about its precise location and biogenesis. Here, we develop a base-resolution m<sup>1</sup>A profiling method, based on m<sup>1</sup>A-induced misincorporation during reverse transcription, and report distinct classes of m<sup>1</sup>A methylome in the human transcriptome. m<sup>1</sup>A in 5' UTR, particularly those at the mRNA cap, associate with increased translation efficiency. A different, small subset of m<sup>1</sup>A exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome, and are dependent on the methyltransferase TRMT6/61A. Additionally, we show that m<sup>1</sup>A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m<sup>1</sup>A level via TRMT61B, a mitochondria-localizing m<sup>1</sup>A methyltransferase, demonstrates that m<sup>1</sup>A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m<sup>1</sup>A methylome and provide a resource for functional studies of m<sup>1</sup>A-mediated epitranscriptomic regulation.