A 3 ' UTR Pumilio-Binding Element Directs Translational Activation in Olfactory Sensory Neurons

Cellular and Developmental Biology Program, 1 Shields Drive, University of California, Davis, Davis, CA 95616, USA.
Neuron (Impact Factor: 15.05). 02/2009; 61(1):57-70. DOI: 10.1016/j.neuron.2008.11.012
Source: PubMed


Prolonged stimulation leads to specific and stable changes in an animal's behavior. In interneurons, this plasticity requires spatial and temporal control of neuronal protein synthesis. Whether such translational control occurs in sensory neurons is not known. Adaptation of the AWC olfactory sensory neurons of C. elegans requires the cGMP-dependent protein kinase EGL-4. Here, we show that the RNA-binding PUF protein FBF-1 is required in the adult AWC for adaptation. In the odor-adapted animal, it increases translation via binding to the egl-4 3' UTR. Further, the PUF protein may localize translation near the sensory cilia and cell body. Although the RNA-binding PUF proteins have been shown to promote plasticity in development by temporally and spatially repressing translation, this work reveals that in the adult nervous system, they can work in a different way to promote experience-dependent plasticity by activating translation in response to environmental stimulation.

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Available from: Noelle l'etoile, May 08, 2014
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    • "Function and Regulation of the PUF Family of RNA-Binding Proteins Previous studies of PUF proteins have suggested they promote degradation of bound mRNAs (Goldstrohm et al., 2007; Kershner and Kimble, 2010; Olivas and Parker, 2000), promote their translation (Archer et al., 2009; Kaye et al., 2009), or exert dual, opposing roles on their target transcripts (Suh et al., 2009). For yeast Puf3p, it has been proposed to promote degradation of its target mRNAs in glucose, but not under non-fermentable carbon sources (Miller and Olivas, 2011; Miller et al., 2014). "
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    ABSTRACT: PUF proteins are post-transcriptional regulators that bind to the 3' UTRs of mRNA transcripts. Herein, we show how a yeast PUF protein, Puf3p, responds to glucose availability to switch the fate of its bound transcripts that encode proteins required for mitochondrial biogenesis. Upon glucose depletion, Puf3p becomes heavily phosphorylated within its N-terminal region of low complexity, associates with polysomes, and promotes translation of its target mRNAs. Such nutrient-responsive phosphorylation toggles the activity of Puf3p to promote either degradation or translation of these mRNAs according to the needs of the cell. Moreover, activation of translation of pre-existing mRNAs might enable rapid adjustment to environmental changes without the need for de novo transcription. Strikingly, a Puf3p phosphomutant no longer promotes translation but becomes trapped in intracellular foci in an mRNA-dependent manner. Our findings suggest that the inability to properly resolve Puf3p-containing RNA-protein granules via a phosphorylation-based mechanism might be toxic to a cell. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 06/2015; 11(10). DOI:10.1016/j.celrep.2015.05.014 · 8.36 Impact Factor
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    • "The cGMP-dependent protein kinase EGL-4 is necessary for olfactory adaptation of the AWC neuronal response (36), and butanone adaptation requires increased translation of egl-4 mRNA, which is facilitated by the RNA-binding protein, FBF-1 (34). Strains that lack fbf-1 are adaptation defective because they fail to up-regulate the kinase EGL-4. "
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    ABSTRACT: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a severe neurodegenerative disorder that affects carriers of premutation CGG-repeat expansion alleles of the fragile X mental retardation 1 (FMR1) gene; current evidence supports a causal role of the expanded CGG repeat within the FMR1 mRNA in the pathogenesis of FXTAS. Though the mRNA has been observed to induce cellular toxicity in FXTAS, the mechanisms are unclear. One common neurophysiological characteristic of FXTAS patients is their inability to properly attenuate their response to an auditory stimulus upon receipt of a small pre-stimulus. Therefore, to gain genetic and cell biological insight into FXTAS, we examined the effect of expanded CGG repeats on the plasticity of the olfactory response of the genetically tractable nematode, Caenorhabditis elegans (C. elegans). While C. elegans is innately attracted to odors, this response can be downregulated if the odor is paired with starvation. We found that expressing expanded CGG repeats in olfactory neurons interfered with this plasticity without affecting either the innate odor-seeking response or the olfactory neuronal morphology. Interrogation of three RNA regulatory pathways indicated that the expanded CGG repeats act via the C. elegans microRNA (miRNA)-specific Argonaute ALG-2 to diminish olfactory plasticity. This observation suggests that the miRNA-Argonaute pathway may play a pathogenic role in subverting neuronal function in FXTAS.
    Human Molecular Genetics 05/2014; 23(18). DOI:10.1093/hmg/ddu210 · 6.39 Impact Factor
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    • "PUF proteins play various roles in RNA metabolism. Although some have roles in ribosomal RNA synthesis and processing [6], [7], the majority of publications focus on the ability of PUF proteins to destabilise, or repress translation of, target mRNAs [8], [9], [10]. The cytoplasmic Saccharomyces cerevisiae PUF proteins are not required for growth on rich media; indeed, S. cerevisiae strains lacking all five cytoplasmic PUF proteins Puf1–5 are viable, despite showing differences in the abundances of some transcripts [11]. "
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    ABSTRACT: PUF proteins are a conserved family of RNA binding proteins found in all eukaryotes examined so far. This study focussed on PUF5, one of 11 PUF family members encoded in the Trypanosoma brucei genome. Native PUF5 is present at less than 50000 molecules per cell in both bloodstream and procyclic form trypanosomes. C-terminally myc-tagged PUF5 was mainly found in the cytoplasm and could be cross-linked to RNA. PUF5 knockdown by RNA interference had no effect on the growth of bloodstream forms. Procyclic forms lacking PUF5 grew normally, but expression of PUF5 bearing a 21 kDa tandem affinity purification tag inhibited growth. Knockdown of PUF5 did not have any effect on the ability of trypanosomes to differentiate from the mammalian to the insect form of the parasite.
    PLoS ONE 10/2013; 8(10):e77371. DOI:10.1371/journal.pone.0077371 · 3.23 Impact Factor
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