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Nature communications
Published

Axonal RNA localization is essential for long-term memory

Authors

Bruna R de Queiroz, Hiba Laghrissi, Seetha Rajeev, Lauren Blot, Fabienne De Graeve, Marine Dehecq, Martina Hallegger, Ugur Dag, Marion Dunoyer de Segonzac, Mirana Ramialison, Chantal Cazevieille, Krystyna Keleman, Jernej Ule, Arnaud Hubstenberger, Florence Besse

Abstract

Nat Commun. 2025 Mar 15;16(1):2560. doi: 10.1038/s41467-025-57651-7.

ABSTRACT

Localization of mRNAs to neuronal terminals, coupled to local translation, has emerged as a prevalent mechanism controlling the synaptic proteome. However, the physiological regulation and function of this process in the context of mature in vivo memory circuits has remained unclear. Here, we combined synaptosome RNA profiling with whole brain high-resolution imaging to uncover mRNAs with different localization patterns in the axons of Drosophila Mushroom Body memory neurons, some exhibiting regionalized, input-dependent, recruitment along axons. By integrating transcriptome-wide binding approaches and functional assays, we show that the conserved Imp RNA binding protein controls the transport of mRNAs to Mushroom Body axons and characterize a mutant in which this transport is selectively impaired. Using this unique mutant, we demonstrate that axonal mRNA localization is required for long-term, but not short-term, behavioral memory. This work uncovers circuit-dependent mRNA targeting in vivo and demonstrates the importance of local RNA regulation in memory consolidation.

PMID:40089499 | DOI:10.1038/s41467-025-57651-7

UK DRI Authors

Jernej Ule profile

Prof Jernej Ule

Centre Director

Deciphering the role of RNA in amyotrophic lateral sclerosis and frontotemporal dementia

Prof Jernej Ule