Novel mRNA-silencing bodies at the synapse: A never-ending story

Thomas, María Gabriela; Boccaccio, Graciela Lidia

doi:10.1080/19420889.2016.1139251

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Neuronal RNP granules are not uniform in composition and properties, but rather belong to a heterogeneous and dynamic collection of entities that coexist to regulate with a high spatiotemporal resolution the fate of associated target mRNAs . Pioneer characterization of the protein content of neuronal RNP granules isolated by differential centrifugation enabled the identification of granule markers, but did not characterize the diversity of individual granule contents.…”

Section: A Heterogenous Collection Of Granulesmentioning

confidence: 99%

Neuronal ribonucleoprotein granules: Dynamic sensors of localized signals

Formicola

Vijayakumar

Besse

2019

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Membrane-less organelles, because of their capacity to dynamically, selectively and reversibly concentrate molecules, are very well adapted for local information processing and rapid response to environmental fluctuations. These features are particularly important in the context of neuronal cells, where synapse-specific activation, or localized extracellular cues, induce signaling events restricted to specialized axonal or dendritic subcompartments. Neuronal ribonucleoprotein (RNP) particles, or granules, are nonmembrane bound macromolecular condensates that concentrate specific sets of mRNAs and regulatory proteins, promoting their long-distance transport to axons or dendrites. Neuronal RNP granules also have a dual function in regulating the translation of associated mRNAs: while preventing mRNA translation at rest, they fuel local protein synthesis upon activation. As revealed by recent work, rapid and reversible switches between these two functional modes are triggered by modifications of the networks of interactions underlying RNP granule assembly. Such flexible properties also come with a cost, as neuronal RNP granules are prone to transition into pathological aggregates in response to mutations, aging, or cellular stresses, further emphasizing the need to better understand the mechanistic principles governing their dynamic assembly and regulation in living systems. K E Y W O R D S biological condensates, local translation, neuronal compartments, neuronal RNA granule, RNP complex 1 | INTRODUCTION Neurons are highly polarized cells specialized in complex information processing, transfer and local storage. They are compartmentalized into macroscopic functional domains-the dendrites, soma and axons-themselves further divided into operational subcompartments locally integrating external signals. 1 These subcompartments are not defined by structural boundaries, but rather by their enrichment in specialized supramolecular complexes. Axon growth cones, for example, are enriched in signaling molecules, components of the protein synthesis and degradation machineries, and cytoskeletal regulators, that together promote physical turning or collapse in response to chemical or mechanical guidance cues. 2,3 Dendritic spines are enriched in postsynaptic proteins such as transmembrane receptors, channels and downstream signal transduction components modulating synaptic strength in response to neuronal activation or inhibition. 4-7Remarkably, neuronal subcompartments are highly plastic and undergo extensive remodeling of their proteomes in response to external cues. 8,9 Such a remodeling involves local protein synthesis of new proteins, a process achieved via the translation activation of localized mRNAs transported from the soma in a translationally silent Nadia Formicola and Jeshlee Vijayakuma contributed equally to this study.

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Section: A Heterogenous Collection Of Granulesmentioning

confidence: 99%

Neuronal ribonucleoprotein granules: Dynamic sensors of localized signals

Formicola

Vijayakumar

Besse

2019

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“…S2" type="url"/>). Even though stress granules have been reported to be widely distributed in many cell types and do not seem to be cell specific, some RNA granules, like SX-bodies (Thomas and Boccaccio, 2016) were only detected in neurons, therefore further work will be required to determine if there are different types of stress granules and if some of these could be cell-specific. We observed that knocking down the expression of P54a or P54b with morpholinos prevented the formation of stress granules in heat-shock conditions, as detected by the anti-TIAL-1 antibody.…”

Section: Discussionmentioning

confidence: 99%

Zebrafish P54 RNA helicases are cytoplasmic granule residents that are required for development and stress resilience

et al. 2016

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Stress granules are cytoplasmic foci that directly respond to the protein synthesis status of the cell. Various environmental insults, such as oxidative stress or extreme heat, block protein synthesis; consequently, mRNA will stall in translation, and stress granules will immediately form and become enriched with mRNAs. P54 DEAD box RNA helicases are components of RNA granules such as P-bodies and stress granules. We studied the expression, in cytoplasmic foci, of both zebrafish P54 RNA helicases (P54a and P54b) during development and found that they are expressed in cytoplasmic granules under both normal conditions and stress conditions. In zebrafish embryos exposed to heat shock, some proportion of P54a and P54b helicases move to larger granules that exhibit the properties of genuine stress granules. Knockdown of P54a and/or P54b in zebrafish embryos produces developmental abnormalities restricted to the posterior trunk; further, these embryos do not form stress granules, and their survival upon exposure to heat-shock conditions is compromised. Our observations fit the model that cells lacking stress granules have no resilience or ability to recover once the stress has ended, indicating that stress granules play an essential role in the way organisms adapt to a changing environment.

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“…Conversely, the aggregation of S-foci is also related to whether the contained polyadenylated mRNAs are released from polysomes, suggesting that repressed mRNAs cycle between S-foci and polysomes [ 32 , 52 ]. Moreover, mammalian Smaug1 is expressed in the process of synaptogenesis, and Smaug1 deletion affects the number and size of synapses, which indicating that Smaug1 regulates local protein translation and affects synapse formation and stability [ 50 , 53 ]. These findings reveal a role for mammalian Smaug1 in the RNA granule formation and translational regulation of SRE-containing mRNAs in neurons.…”

Section: Biological Functions Of Samd4mentioning

confidence: 99%

RNA binding protein SAMD4: current knowledge and future perspectives

Wang

Zhang

2023

Cell Biosci

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SAMD4 protein family is a class of novel RNA-binding proteins that can mediate post-transcriptional regulation and translation repression in eukaryotes, which are highly conserved from yeast to humans during evolution. In mammalian cells, SAMD4 protein family consists of two members including SAMD4A/Smaug1 and SAMD4B/Smaug2, both of which contain common SAM domain that can specifically bind to different target mRNAs through stem-loop structures, also known as Smaug recognition elements (SREs), and regulate the mRNA stability, degradation and translation. In addition, SAMD4 can form the cytoplasmic mRNA silencing foci and regulate the translation of SRE-containing mRNAs in neurons. SAMD4 also can form the cytosolic membrane-less organelles (MLOs), termed as Smaug1 bodies, and regulate mitochondrial function. Importantly, many studies have identified that SAMD4 family members are involved in various pathological processes including myopathy, bone development, neural development, and cancer occurrence and progression. In this review, we mainly summarize the structural characteristics, biological functions and molecular regulatory mechanisms of SAMD4 protein family members, which will provide a basis for further research and clinical application of SAMD4 protein family.

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Novel mRNA-silencing bodies at the synapse: A never-ending story

Cited by 4 publications

References 31 publications

Neuronal ribonucleoprotein granules: Dynamic sensors of localized signals

Neuronal ribonucleoprotein granules: Dynamic sensors of localized signals

Zebrafish P54 RNA helicases are cytoplasmic granule residents that are required for development and stress resilience

RNA binding protein SAMD4: current knowledge and future perspectives

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