Modulation of N-terminal methyltransferase 1 by an N6-methyladenosine-based epitranscriptomic mechanism

Abstract

Protein α-N-methylation is an evolutionarily conserved type of post-translational modification; however, little is known about the regulatory mechanisms for this modification. Methylation at the N⁶ position of adenosine in mRNAs is dynamic and modulates their stability, splicing, and translational efficiency. Here, we found that the expression of N-terminal methyltransferase 1 (NTMT1) protein is altered by depletion of those genes encoding the reader/writer/eraser proteins of N⁶-methyladenosine (m⁶A). We also observed that MRG15 is N-terminally methylated by NTMT1, and this methylation could also be modulated by reader/writer/eraser proteins of m⁶A. Together, these results revealed a novel m⁶A-based epitranscriptomic mechanism in regulating protein N-terminal methylation.

Keywords: Epitranscriptomics; Mass spectrometry; N-terminal methylation; N6-methyladenosine; Post-translational modification; RNA modification.