Far from home: the role of glial mRNA localization in synaptic plasticity

RNA, Journal Year: 2022, Volume and Issue: 29(2), P. 153 - 169

Published: Nov. 28, 2022

Neurons and glia are highly polarized cells, whose distal cytoplasmic functional subdomains require specific proteins. have axonal dendritic extensions containing synapses plasticity is regulated efficiently by mRNA transport localized translation. The principles behind these mechanisms equally attractive for explaining rapid local regulation of glial projections, independent their cell nucleus. However, in contrast to neurons, localization has received little experimental attention glia. Nevertheless, there many functionally diverse subtypes extensive networks long projections with likely that influence neurons synapses. Moreover, other neuron-like properties, including electrical activity, secretion gliotransmitters calcium signaling, influencing, example, synaptic transmission, axon pruning. Here, we review previous studies concerning transcripts important roles influencing plasticity, focusing on a few cases involving We discuss variety questions about translation remain be addressed, using cutting-edge tools already available neurons.

Language: Английский

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The Novel Role of Midbody-Associated mRNAs in Regulating Abscission

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 28, 2022

Abstract Midbodies (MBs) have been shown to function during telophase as a recruiting hub, especially for ESCRT-III complex subunits, regulate the abscission step of cytokinesis. However, molecular machinery governing specific protein targeting and activation at MB remains poorly understood. Until recently, it was thought that regulating proteins, such accumulate by directly or indirectly binding resident protein, CEP55. recent studies depletion CEP55 does not fully block MB, cells in knock-out mice divide normally. Additionally, since MBs are microtubule-rich, proteinaceous structures, is conceptually hard imagine how large complexes, complex, can successfully diffuse into from cytosol rapid highly regulated manner. Here, we show contain mRNAs these MB-associated be locally translated, resulting accumulation abscission-regulating proteins. We also demonstrate localized translation CHMP4B required its site 3′ UTR-dependent mRNA successful completion Finally, identify regulatory cis -elements within RNAs necessary sufficient trafficking MB. Based on all this data, propose novel method cytokinesis selective mRNAs.

Language: Английский

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Murine glial protrusion transcripts predict localized Drosophila glial mRNAs involved in plasticity

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(10)

Published: July 22, 2024

The polarization of cells often involves the transport specific mRNAs and their localized translation in distal projections. Neurons glia are both known to contain long cytoplasmic processes, while transcripts have only been studied extensively neurons, not glia, especially intact nervous systems. Here, we predict 1,740 Drosophila glial by extrapolating from our meta-analysis seven existing studies characterizing transcriptomes translatomes synaptically associated mammalian glia. We demonstrate that localization projections strongly predicts high-confidence homologs larval motor neuron–associated highly statistically enriched for genes with neurological diseases. further show some these specifically required structural plasticity at nearby neuromuscular junction synapses. conclude peripheral mRNA is a common conserved phenomenon propose it likely be functionally important disease.

Language: Английский

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

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

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

Language: Английский

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The RNA binding protein HNRNPA2B1 regulates RNA abundance and motor protein activity in neurites

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 26, 2024

ABSTRACT RNA molecules are localized to subcellular regions through interactions between localization-regulatory cis-elements and trans-acting binding proteins (RBPs). However, the identities of RNAs whose localization is regulated by a specific RBP as well impacts that on cell function have generally remained unknown. Here, we demonstrate HNRNPA2B1 acts keep out neuronal projections. Using fractionation, high-throughput sequencing, single molecule FISH, find hundreds markedly increased abundance in neurites knockout cells. These often encode motor enriched for known sites motifs their 3′ UTRs. The speed processivity microtubule-based transport impaired these cells, specifically neurites. point mutations increase its cytoplasmic relative wildtype lead stronger suppression mislocalization defects than seen with HNRNPA2B1. We further localizations target sensitive perturbations decay machinery, suggesting it HNRNPA2B1’s role regulating stability may explain observations. findings establish negative regulator neurite link activities them.

Language: Английский

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