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<p>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 <i>pumilio</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月21日

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

摘要

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.