Smaug1 mRNA-silencing foci respond to NMDA and modulate synapse formation

Báez, María Verónica; Luchelli, Luciana; Maschi, Darío; Habif, Martín; Pascual, Malena Lucía; Thomas, María Gabriela; Boccaccio, Graciela Lidia

doi:10.1083/jcb.201108159

Cited by 51 publications

(122 citation statements)

References 110 publications

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“…Similar to the SX-bodies, the S-foci and the FMRP-positive granules transiently dissolved upon DHPG, although with different kinetics. In striking contrast to the enhanced formation of the SX-bodies upon NMDAR stimulation, the S-foci dissolved and the FMRP-positive granules did not respond to NMDA, as reported previously (Antar et al, 2004;Baez et al, 2011). The size and number of XRN-1-positive bodies were affected by drugs that stabilize polysomes, suggesting that transcripts released from polysomes upon NMDAR stimulation are directed to the XRN1 bodies.…”

Section: Introductionmentioning

confidence: 44%

“…As expected, NMDAR stimulation provoked a reduction in the incorporation of HPG, indicating a reduced local translation rate ( Fig. 4A,B; Baez et al, 2011). By contrast, a DHPG pulse increased the incorporation of HPG by a factor of two.…”

Section: Xrn1 Forms Synaptic Bodies That Are Different From Processinmentioning

confidence: 73%

“…First, we monitored the local changes in the protein synthesis rate upon a short stimulation with 30 mM NMDA or 100 mM DHPG, which stimulates metabotropic receptors. We treated cultured hippocampal neurons with agonists as reported previously (Antar et al, 2004;Cougot et al, 2008;Park et al, 2008;Zeitelhofer et al, 2008;Baez et al, 2011;Tatavarty et al, 2012;Graber et al, 2013). We treated the neurons with tetrodotoxin (TTX), a drug that blocks voltagegated sodium channels and spontaneous activity, and then we exposed the cells to a 5-minute pulse of 30 mM NMDA or 100 mM DHPG (see Materials and Methods).…”

Section: Xrn1 Forms Synaptic Bodies That Are Different From Processinmentioning

confidence: 99%

“…NMDAR stimulation enhanced SX-body formation and inhibited translation at spines and dendrites, whereas mGluR activation provoked the dissolution of the SX-bodies and stimulated local translation. We compared the behavior of the SX-bodies to that of S-foci and FMRP-positive granules, also involved in translational regulation at the synapse (Antar et al, 2004;Baez et al, 2011;Darnell et al, 2011;Graber et al, 2013). Similar to the SX-bodies, the S-foci and the FMRP-positive granules transiently dissolved upon DHPG, although with different kinetics.…”

Section: Introductionmentioning

confidence: 99%

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Synaptic control of mRNA translation by reversible assembly of XRN1 bodies

Luchelli¹,

Thomas²,

Boccaccio³

2015

Journal of Cell Science

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Repression of mRNA translation is linked to the formation of specific cytosolic foci such as stress granules and processing bodies, which store or degrade mRNAs. In neurons, synaptic activity regulates translation at the post-synapse and this is important for plasticity. Nmethyl-D-aspartate (NMDA) receptor stimulation downregulates translation, and we speculate that this is linked to the formation of unknown mRNA-silencing foci. Here, we show that the 59-39 exoribonuclease XRN1 forms discrete clusters associated with the post-synapse that are different from processing bodies or stress granules, and we named them synaptic XRN1 bodies (SX-bodies). Using primary neurons, we found that the SX-bodies respond to synapse stimulation and that their formation correlates inversely with the local translation rate. SX-bodies increase in size and number upon NMDA stimulation, and metabotropic glutamate receptor activation provokes SX-body dissolution, along with increased translation. The response is specific and the previously described Smaug1 foci and FMRP granules show a different response. Finally, XRN1 knockdown impairs the translational repression triggered by NMDA. Collectively, these observations support a role for the SX-bodies in the reversible masking and silencing of mRNAs at the synapse.

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Section: Introductionmentioning

confidence: 44%

Section: Xrn1 Forms Synaptic Bodies That Are Different From Processinmentioning

confidence: 73%

Section: Xrn1 Forms Synaptic Bodies That Are Different From Processinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synaptic control of mRNA translation by reversible assembly of XRN1 bodies

Luchelli¹,

Thomas²,

Boccaccio³

2015

Journal of Cell Science

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“…For example, when ectopically expressed in mammalian cells, Samd4 formed cytoplasmic granules containing polyadenylated RNA and markers of stress granules (6). Samd4 was also reportedly detected in neuronal dendrites, within mRNA-silencing foci that disassembled in response to the neurotransmitter Nmethyl-D-aspartate (7). Recently, Samd4 overexpression was shown to suppress hallmarks of myotonic dystrophy-1 (DM1; Online Mendelian Inheritance in Man no.…”

Section: Akt/pkb | N-ethyl-n-nitrosoureamentioning

confidence: 99%

Mutation of mouse Samd4 causes leanness, myopathy, uncoupled mitochondrial respiration, and dysregulated mTORC1 signaling

Chen

Holland

Shelton³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Whereas many heritable obesity phenotypes are known, lean phenotypes are comparatively uncommon. Yet they can reveal critical checkpoints regulating energy balance. During a large-scale random germ-line mutagenesis project, we identified mice with a lean phenotype, myopathy, excessive energy expenditure despite diminished cage activity, and impaired glucose tolerance. This phenotype, termed “ supermodel, ” was strictly recessive and was ascribed to a missense mutation in Sterile alpha motif domain containing protein 4 ( Samd4 ), a gene encoding an RNA-binding protein with no previously known function in mammals. This study provides evidence that Samd4 modulates the activities of the mechanistic target of rapamycin complex 1, a master regulator of metabolism.

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Regulation of Translationally Repressed mRNAs in Zebrafish and Mouse Oocytes

Kotani

Maehata

Takei

2017

Results and Problems in Cell Differentiation

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From the beginning of oogenesis, oocytes accumulate tens of thousands of mRNAs for promoting oocyte growth and development. A large number of these mRNAs are translationally repressed and localized within the oocyte cytoplasm. Translational activation of these dormant mRNAs at specific sites and timings plays central roles in driving progression of the meiotic cell cycle, axis formation, mitotic cleavages, transcriptional initiation, and morphogenesis. Regulation of the localization and temporal translation of these mRNAs has been shown to rely on cis-acting elements in the mRNAs and trans-acting factors recognizing and binding to the elements. Recently, using model vertebrate zebrafish, localization itself and formation of physiological structures such as RNA granules have been shown to coordinate the accurate timings of translational activation of dormant mRNAs. This subcellular regulation of mRNAs is also utilized in other animals including mouse. In this chapter, we review fundamental roles of temporal regulation of mRNA translation in oogenesis and early development and then focus on the mechanisms of mRNA regulation in the oocyte cytoplasm by which the activation of dormant mRNAs at specific timings is achieved.

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Smaug1 mRNA-silencing foci respond to NMDA and modulate synapse formation

Abstract: S-foci, the first reported mRNA-silencing foci specific to neurons, may control local mRNA translation in response to NMDA receptor stimulation and synaptic plasticity.

Cited by 51 publications

References 110 publications

Synaptic control of mRNA translation by reversible assembly of XRN1 bodies

Synaptic control of mRNA translation by reversible assembly of XRN1 bodies

Mutation of mouse Samd4 causes leanness, myopathy, uncoupled mitochondrial respiration, and dysregulated mTORC1 signaling

Regulation of Translationally Repressed mRNAs in Zebrafish and Mouse Oocytes

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