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

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-02-21 DOI:10.1038/s44319-025-00401-z

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

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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.

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Pumilio与mRNA 3' UTR异构体的差异结合调节突触蛋白的定位。

在神经细胞中，RNA的调控对于基因表达的时空控制至关重要，但突触蛋白的正确定位、水平和功能是如何实现的尚不清楚。在这项研究中，我们在全球范围内研究了替代3' utr在调节果蝇大脑突触区域RNA定位中的作用。我们确定了翻译抑制因子Pumilio的直接mRNA靶标，发现Pumilio结合的mRNA编码突触体中富集的蛋白质。Pumilio与同一基因的RNA异构体不同地结合，倾向于长，神经元的3' utr。这些较长的3' UTR倾向于留在神经元体细胞中，而较短的UTR异构体则定位于突触。在培养的pumilio突变神经元中，轴突生长缺陷伴随着mRNA异构体错定位，这些pumilio靶mRNA编码的蛋白质在突触钮孔处表现出过多的丰度。我们的研究确定了神经元中蛋白质功能时空调节的重要机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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