Modifiers of solid RNP granules control normal RNP dynamics and mRNA activity in early development

Hubstenberger, Arnaud; Cameron, Cristiana; Noble, Scott L.; Keenan, Sean; Evans, Thomas C.

doi:10.1083/jcb.201504044

Cited by 30 publications

(39 citation statements)

References 86 publications

(179 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that the RNA species in the normal, mature axons are translationally repressed until they are activated by the injury. Adaxonal glia may play an important role in this activation of the intrinsic translational machinery in the axon in addition to supplying functional ribosomes.There is ample evidence for such a regulatory mechanism in nature, e.g, in the oocyte where mRNAs are packaged with ribonucleoprotein particles (RNPs) and are translationally repressed by multiple mechanisms until they are activated in later stages of oogenesis (Hubstenberger et al 2015). Many other examples exist in which mRNA binding proteins (RBPs) store mRNAs in inactive forms until regulatory mechanisms are invoked to activate translation (Anderson and Kedersha 2008;Kiebler and Bassell 2006;Thomas et al 2011;Wells 2006).…”

Section: Discussionmentioning

confidence: 99%

Squid Giant Axon Contains Neurofilament Protein mRNA but does not Synthesize Neurofilament Proteins

et al. 2016

View full text Add to dashboard Cite

When isolated squid giant axons are incubated in radioactive amino acids, abundant newly synthesized proteins are found in the axoplasm. These proteins are translated in the adaxonal Schwann cells and subsequently transferred into the giant axon. The question as to whether any de novo protein synthesis occurs in the giant axon itself is difficult to resolve because the small contribution of the proteins possibly synthesized intra-axonally is not easily distinguished from the large amounts of the proteins being supplied from the Schwann cells. In this paper we reexamine this issue by studying the synthesis of endogenous neurofilament (NF) proteins in the axon. Our laboratory previously showed that NF mRNA and protein is present in the squid giant axon, but not in the surrounding adaxonal glia. Therefore, if the isolated squid axon could be shown to contain newly synthesized NF protein de novo, it could not arise from the adaxonal glia. The results of experiments in this paper show that abundant 3H-labeled NF protein is synthesized in the squid giant fiber lobe containing the giant axon's neuronal cell bodies, but despite the presence of NF mRNA in the giant axon, no labeled NF protein is detected in the giant axon. This lends support to the Glia-Axon Protein Transfer Hypothesis which posits that the squid giant axon obtains newly synthesized protein by Schwann cell transfer and not through intra-axonal protein synthesis, and further suggests that the NF mRNA in the axon is in a translationally repressed state.

show abstract

Section: Discussionmentioning

confidence: 99%

Squid Giant Axon Contains Neurofilament Protein mRNA but does not Synthesize Neurofilament Proteins

et al. 2016

View full text Add to dashboard Cite

show abstract

“…For example, VCP, which is associated with both ALS and multisystem proteinopathy (Johnson et al, 2010; Watts et al, 2004), is critical to both RNP granule disassembly and pathological aggregate clearance (Buchan et al, 2013; Ju et al, 2009; Meyer and Weihl, 2014). Moreover, RNA helicases such as Ddx6 may be critical to maintaining fluidity of these compartments, preventing the formation of pathological solids (Hubstenberger et al, 2015; 2013). …”

Section: Liquid-to-solid Phase Transitions In Disease Pathogenesismentioning

confidence: 99%

Prions and Protein Assemblies that Convey Biological Information in Health and Disease

Sanders

Kaufman

Holmes

et al. 2016

Neuron

View full text Add to dashboard Cite

Prions derived from the prion protein (PrP) were first characterized as infectious agents that transmit pathology between individuals. However, the majority of cases of neurodegeneration caused by PrP prions occur sporadically. Proteins that self-assemble as cross-beta sheet amyloids are a defining pathological feature of infectious prion disorders and all major age-associated neurodegenerative diseases. In fact, multiple non-infectious proteins exhibit properties of template-driven self-assembly that are strikingly similar to PrP. Evidence suggests that like PrP, many proteins form aggregates that propagate between cells and convert cognate monomer into ordered assemblies. We now recognize that numerous proteins assemble into macromolecular complexes as part of normal physiology, some of which are self-amplifying. This review highlights similarities among infectious and non-infectious neurodegenerative diseases associated with prions, emphasizing the normal and pathogenic roles of higher-order protein assemblies. We propose that studies of the structural and cellular biology of pathological vs. physiological aggregates will be mutually informative.

show abstract

“…Y2H data indicated that B0035.6 interacts with DEPS-1 via its C-terminal region ( Figure S3A). B0035.6 has no predicted conserved domain structures but a low similarity to human MEG-3 (Hubstenberger et al, 2015). B0035.6 was also one of the significant interactors of PRG-1 in our proteomic analysis (Table S1, Figure S3B), suggesting DEPS-1, B0035.6 and PRG-1 form a trimeric complex.…”

Section: Edg-1 Interacts With Both Deps-1 and Prg-1 And Modulates Depmentioning

confidence: 91%

Direct interaction of PIWI and DEPS-1 is essential for piRNA function and condensate ultrastructure inCaenorhabditis elegans

Braukmann

Butler

et al. 2019

Preprint

View full text Add to dashboard Cite

Membraneless organelles are platforms for many aspects of RNA biology including small non-coding RNA (ncRNA) mediated gene silencing. How small ncRNAs utilise phase separated environments for their function is unclear. To address this question, we investigated how the PIWI-interacting RNA (piRNA) pathway engages with the membraneless organelle P granule in Caenorhabditis elegans. Proteomic analysis of the PIWI protein PRG-1 revealed an interaction with the constitutive P granule 2 protein DEPS-1. Furthermore we identified a novel motif on DEPS-1, PBS, which interacts directly with the Piwi domain of PRG-1. This protein complex forms intertwining ultrastructures to build elongated condensates in vivo. These suborganelle ultrastructures depend on the Piwi-interacting motif of DEPS-1 and mediate piRNA function. Additionally, we identify a novel interactor of DEPS-1, EDG-1, which is required for DEPS-1 condensates to form correctly. We show that DEPS-1 is not required for piRNA biogenesis but piRNA function: deps-1 mutants fail to produce the secondary endo-siRNAs required for the silencing of piRNA targets. Our study reveals how specific protein-protein interactions drive the spatial organisation and function of small RNA pathways within membraneless organelles.as the P-bodies and germ granules (Eulalio et al., 2007;Voronina et al., 2011).

show abstract

Modifiers of solid RNP granules control normal RNP dynamics and mRNA activity in early development

Abstract: Modifiers of aberrant solid RNP granules suggest new insights into pathways that control dynamics of large-scale RNP bodies and mRNAs during C. elegans oogenesis.

Cited by 30 publications

References 86 publications

Squid Giant Axon Contains Neurofilament Protein mRNA but does not Synthesize Neurofilament Proteins

Squid Giant Axon Contains Neurofilament Protein mRNA but does not Synthesize Neurofilament Proteins

Prions and Protein Assemblies that Convey Biological Information in Health and Disease

Direct interaction of PIWI and DEPS-1 is essential for piRNA function and condensate ultrastructure inCaenorhabditis elegans

Contact Info

Product

Resources

About