DataVXAdvanced SciencePaper
journal article·2025-12Open access

Enhanced Protein Synthesis and Hippocampus‐Dependent Memory via Inhibition of YTHDF2 ‐Mediated m 6 A mRNA Degradation

Kuan Li, Chen Guo, Xiaoli Wu, Cuiting Wu, Songfen Wu, Si Su, Min Wu, Xidan Zhou, Si Li, Yihui Cui, Tao Zhou

Advanced Science· Volume 12· Issue 45
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Abstract

Abstract N 6 ‐methyladenosine (m 6 A) modification intricately regulates mRNA transportation, localization, and translation, significantly influencing learning and memory processes. However, the specific role of YT521‐B homology (YTH) domain‐containing family protein 2 ( YTHDF2) ‐mediated m 6 A mRNA degradation in learning and memory remains elusive. Utilizing a forebrain‐specific conditional knockout mice model, it is discovered that the absence of YTHDF2 impedes the decay of m 6 A‐modified mRNAs, resulting in heightened synaptic transmission in hippocampal neurons and improved hippocampus‐dependent learning and memory. Unexpectedly, an increase in activity‐dependent protein synthesis is also observed. Reintroduction of YTHDF2 expression or reduction of its downstream target, Semaphorin 4B ( SEMA4B) , in the hippocampus reverses the enhanced memory in conditional knockout mice, while augmenting YTHDF2 in wild‐type mice impairs memory performance. These findings underscore the pivotal role of YTHDF2 ‐mediated mRNA degradation in regulating learning and memory processes.
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Research context

OpenAlex topics: RNA modifications and cancer · RNA Research and Splicing · RNA and protein synthesis mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pharmacy Shenzhen People's Hospital (The Second Clinical Medical College Jinan University The First Affiliated Hospital) Southern University of Science and Technology Shenzhen 518055 China

Department of Neurology of Sir Run Run Shaw Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Hangzhou 310058 China

Shenzhen Neher Neural Plasticity Laboratory Shenzhen Key Laboratory of Drug Addiction the Brain Cognition and Brain Disease Institute Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China

Shenzhen Institutes of Advanced Technology University of Chinese Academy of Sciences Beijing 100049 China

Faculty of Life and Health Sciences Shenzhen University of Advanced Technology Shenzhen 518106 China

Shenzhen‐Hong Kong Institute of Brain Science‐Shenzhen Fundamental Research Institutions Shenzhen 518055 China

Funding

National Natural Science Foundation of China · Shenzhen Science and Technology Innovation Program · Basic and Applied Basic Research Foundation of Guangdong Province

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