Enhanced Protein Synthesis and Hippocampus-Dependent Memory via Inhibition of YTHDF2-Mediated m⁶A mRNA Degradation.

ABSTRACT: N⁶-methyladenosine (m⁶A) 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 m⁶A 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 m⁶A-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 downst

SUBMITTER: Li K 

PROVIDER: S-EPMC12677670 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature