Shuangshuang Feng1,2,3, Maitena Tellaetxe-Abete4,7, Yujie Zhang2,3,7, Yan Peng2,3,5, Han Zhou2, Mingjie Dong2, Erika Larrea2,3,6, Liang Xue2,3, Li Zhang2 and Magdalena J. Koziol1,2,3 1State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China; 2Chinese Institute for Brain Research, Beijing 102206, China; 3Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing 102206, China; 4Intelligent Systems Group, Computer Science Faculty, University of the Basque Country, Donostia/San Sebastian 20018, Spain; 5Peking University, Beijing, 100871, China; 6Tsinghua University, Beijing 100084, China

↵7 These authors contributed equally to this work.

Corresponding author: mjkcibr.ac.cn Abstract

N6-Methyladenosine (m6A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m6A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remains poorly understood. We investigated m6A in the hippocampus at a single-cell resolution, revealing a comprehensive landscape of m6A modifications within individual cells. Through our analysis, we uncovered transcripts exhibiting a dense m6A profile, notably linked to neurological disorders such as Alzheimer's disease. Our findings suggest a pivotal role of m6A-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 m6A RNA methylation in the healthy and diseased brain.

Footnotes

[Supplemental material is available for this article.]

Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.278424.123.

Freely available online through the Genome Research Open Access option.

Received August 21, 2023. Accepted June 11, 2024.