Pumilio differentially binds to mRNA 3′ UTR isoforms to regulate localization of synaptic proteins
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.
Authors
- Carlos Alfonso-Gonzalez
- Stylianos Tsagkris (ORCID: https://orcid.org/0000-0003-1698-8757)
- Andreas Vlachos (ORCID: https://orcid.org/0000-0002-2646-3770)
- Andrew Rezansoff
- Dominika Grzejda (ORCID: https://orcid.org/0000-0002-2946-0081)
- Valérie Hilgers (ORCID: https://orcid.org/0000-0002-4551-0931)
- F.‐Nora Vögtle (ORCID: https://orcid.org/0000-0002-5062-3287)
- Judit Carrasco (ORCID: https://orcid.org/0000-0002-4619-9452)
- Hasan Can Ozbulut (ORCID: https://orcid.org/0009-0007-0677-2967)
- Lena Neuhaus
- Sakshi Gorey
- Mengjin Shi
Institutions
- Roche (Switzerland) (CH)
- University of Freiburg (DE)
- Heidelberg University (DE)
- AstraZeneca (Australia) (AU)
- European Molecular Biology Laboratory (IT)
- Heidelberg Engineering (Germany) (DE)
- European Molecular Biology Laboratory (DE)
- AstraZeneca (Germany) (DE)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- Heidelberg University (US)
Publication Details
- Journal
- EMBO Reports
- Published
- 2025-02-21
- DOI
- https://doi.org/10.1038/s44319-025-00401-z
- Citations
- 5
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Max-Planck-Gesellschaft
- National Institutes of Health
- European Research Council