Single-cell discovery of m 6 A RNA modifications in the hippocampus.

N ⁶ -Methyladenosine (m ⁶ A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m ⁶ A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remains poorly understood. We investigated m ⁶ A in the hippocampus at a single-cell resolution, revealing a comprehensive landscape of m ⁶ A modifications within individual cells. Through our analysis, we uncovered transcripts exhibiting a dense m ⁶ A profile, notably linked to neurological disorders such as Alzheimer's disease. Our findings suggest a pivotal role of m ⁶ A-containing transcripts, particularly in the context of CAMK2A neurons. Overall, this work provides new insights into the molecular mechanisms underlying hippocampal physiology and lays the foundation for future studies investigating the dynamic nature of m ⁶ A RNA methylation in the healthy and diseased brain.
(© 2024 Feng et al.; Published by Cold Spring Harbor Laboratory Press.)