Pumilio differentially binds to mRNA 3′ UTR isoforms to regulate localization 
of synaptic proteins

Grzejda, Dominika; Hess, Anton; Rezansoff, Andrew; Gorey, Sakshi; Carrasco, Judit; Alfonso-Gonzalez, Carlos; Tsagkris, Stylianos; Neuhaus, Lena; Shi, Mengjin; Ozbulut, Hasan Can; Vögtle, Friederike-Nora; Vlachos, Andreas; Hilgers, Valérie

doi:10.1038/s44319-025-00401-z

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Pumilio differentially binds to mRNA 3′ UTR isoforms to regulate localization of synaptic proteins

MPS-Authors

Grzejda, Dominika
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hess, Anton
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Rezansoff, Andrew
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Gorey, Sakshi
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Carrasco, Judit
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Alfonso-Gonzalez, Carlos
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Tsagkris, Stylianos
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Neuhaus, Lena
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Shi, Mengjin
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Ozbulut, Hasan Can
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Hilgers, Valérie
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Grzejda, D., Hess, A., Rezansoff, A., Gorey, S., Carrasco, J., Alfonso-Gonzalez, C., et al. (2025). Pumilio differentially binds to mRNA 3′ UTR isoforms to regulate localization of synaptic proteins. EMBO Reports. doi:10.1038/s44319-025-00401-z.

Cite as: https://hdl.handle.net/21.11116/0000-0010-EA8D-8

Abstract

In neuronal cells, the regulation of RNA is crucial for the spatiotemporal control of gene expression, but how the correct localization, levels, and function of synaptic proteins are achieved is not well understood. In this study, we globally investigate the role of alternative 3′ UTRs in regulating RNA localization in the synaptic regions of the Drosophila brain. We identify direct mRNA targets of the translational repressor Pumilio, finding that mRNAs bound by Pumilio encode proteins enriched in synaptosomes. Pumilio differentially binds to RNA isoforms of the same gene, favoring long, neuronal 3′ UTRs. These longer 3′ UTRs tend to remain in the neuronal soma, whereas shorter UTR isoforms localize to the synapse. In cultured pumilio mutant neurons, axon outgrowth defects are accompanied by mRNA isoform mislocalization, and proteins encoded by these Pumilio target mRNAs display excessive abundance at synaptic boutons. Our study identifies an important mechanism for the spatiotemporal regulation of protein function in neurons.