Investigating N3-methylcytosine Modification: Implications for Synaptic Regulation

Abstract

The present investigation focuses on the roles and locations of m3C RNA modifications in cellular systems, with a particular emphasis on their impact on neuronal plasticity. Historically, m3C modifications have been predominantly and narrowly attributed to mitochondrial tRNA. Such a limited perspective, however, undeniably raises fundamental questions, especially given the restricted understanding of m3C's broader distribution across diverse RNA categories. To address this significant lacuna in our knowledge, the current research embarks on a meticulous and exhaustive examination. This rigorous investigation revealed the surprising presence of m3C modifications not only in the expected tRNA but also across other RNA species. This ground-breaking discovery inherently challenges extant paradigms in the vast field of cellular RNA biology, mandating a thorough and comprehensive re-evaluation of previous assumptions. Utilising an analytical approach, the study explored the functional dimensions of highly m3C-modified transcripts. A comparative analysis was executed, differentiating their functionalities between the wild-type and the conditions subsequent to METTL8 deletion, thereby providing a dynamic picture of their behaviour specifically, in synaptic regulation. Furthermore, evaluations were conducted to assess the abundance of m3C modifications beyond the mitochondria under conditions of NMDA receptor activation. This approach provided a more nuanced, in-depth understanding of the findings, shedding light on previously uncharted territories. In the end, the research shows that m3C modifications may play essential roles in a wide range of cellular operations. Moreover, this study provided evidence indicating that the presence of m3C modifications extends beyond the mitochondria. Implications for future studies abound.