Numerous interactions act redundantly to assemble a tunable size of P bodies in
            <i>Saccharomyces cerevisiae</i>

Rao, Bhalchandra S.; Parker, Roy

doi:10.1073/pnas.1712396114

Cited by 89 publications

(127 citation statements)

References 43 publications

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“…The three most enriched P body components, Dcp2, Pat1, and Edc3, are the three major proteins shown to affect P body assembly (Buchan et al, 2008;Decker et al, 2007;Teixeira and Parker, 2007). Other core proteins, Dhh1, Upf1, and the Lsm1-7 complex can contribute to P body assembly as well (Decker et al, 2007;Sheth and Parker, 2006;Hondele et al, 2019;Rao and Parker, 2017). In contrast, none of the non-core components are required for efficient P-body assembly.…”

Section: Assembly Of P Bodies Through Cooperative Interactionsmentioning

confidence: 99%

A quantitative inventory of yeast P body proteins reveals principles of composition and specificity

Xing

Muhlrad

Parker

et al. 2018

Preprint

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P bodies are archetypal biomolecular condensates that concentrate proteins and RNA without a surrounding membrane. While dozens of P body proteins are known, the concentrations of components in the compartment have not been measured. We used live cell imaging to generate a quantitative inventory of the major proteins in yeast P bodies. Only 7 proteins are highly concentrated in P bodies (5.1-15 uM); the 24 others examined are appreciably lower (most ≤ 2.6 uM). P body concentration correlates inversely with cytoplasmic exchange rate. Sequence elements driving Dcp2 concentration into P bodies are distributed across the protein and act cooperatively. Our data indicate that P bodies, and probably other condensates, are biochemically simpler than suggested by proteomic analyses, with implications for specificity, reconstitution and evolution. Currently 124 words (limit = 150)

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Section: Assembly Of P Bodies Through Cooperative Interactionsmentioning

confidence: 99%

A quantitative inventory of yeast P body proteins reveals principles of composition and specificity

Xing

Muhlrad

Parker

et al. 2018

Preprint

Self Cite

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“…Suppression of clathrin deficiency by PSP2 is a striking result. Psp2 is known to localize to RNA granules 19 and upon overexpression, can rescue P-body formation in edc3Δlsm4Δc strain 39 . Scd6 binds TIF4631 (eIF4G1) to repress translation and interestingly Psp2 is reported to physically interact with its paralog TIF4632 40 .…”

Section: Discussionmentioning

confidence: 99%

PSP2, a gene encoding RGG-motif protein, is a novel suppressor of clathrin heavy chain deficiency

Roy

Rajyaguru

2020

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Running title: RGG-motif proteins suppress clathrin heavy chain deficiency. AbstractClathrin, made up of the heavy-and light-chains, constitutes one of the most abundant protein in vesicles involved in intracellular protein trafficking and endocytosis. YPR129W, which encodes RGGmotif containing translation repressor was identified as a part of multi-gene construct (SCD6) that suppressed clathrin deficiency. However, the contribution of YPR129W alone in suppressing clathrin deficiency has not been documented. In this study we identify YPR129W as a necessary and sufficient gene in a multigene construct SCD6 that suppresses clathrin deficiency. Importantly, we identify cytoplasmic RGG-motif protein encoding gene PSP2 as a novel suppressor of clathrin deficiency. Three other RGG-motif protein encoding genes SBP1, DED1 and GBP2 do not suppress clathrin deficiency. DHH1, a DEAD-box RNA helicase with translation repression activity also fails to rescue clathrin deficiency. α-factor secretion assay suggests that suppression of clathrin deficiency by SCD6 and PSP2 is not mediated by the rescue of the trans-Golgi network (TGN) protein sorting defect observed in the absence of CHC1. Detailed domain analysis of the two suppressors reveals that the RGG-motif of both Scd6 and Psp2 is important for suppressing clathrin deficiency. Additionally, the Lsm domain deletion as well as the arginine to alanine mutation in the arginine methylation defective (AMD) mutant render Scd6 defective in suppressing clathrin deficiency. Overall based on our results using SCD6 and PSP2 proteins, we identify a novel role of RGG-motif in suppressing clathrin deficiency. Since both the suppressors are RNA-binding granule-resident proteins, this study opens an exciting avenue for exploring the connection between clathrin function and cytoplasmic RNA metabolism.

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“…This indicates that a 1:1 complex is likely formed between GRN-5 /rGRN-5 and TDP-43CTD, which stabilize the droplets. It is known that the phenomenon of coacervation is dependent on a defined valency of interactions among the molecules which remain fixed within the dense phase (75)(76)(77)(78). The data indicates that a 1:1 stoichiometry of GRN-5: TDP-43CTD could be sufficient to fulfil the required valency of the weak interactions that mediate the LLPS.…”

Section: Grns -3 and -5 Differently Modulate The Llps And Formation Omentioning

confidence: 98%

Granulins modulate liquid-liquid phase separation and aggregation of TDP-43 C-terminal domain

Bhopatkar

Uversky

Rangachari

2019

Preprint

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Tar DNA binding protein (TDP-43) has emerged as a key player in many neurodegenerative pathologies including frontotemporal lobar degeneration (FTLD) and amyotropic lateral sclerosis (ALS). Important hallmarks of FTLD and ALS are the toxic cytoplasmic inclusions of Cterminal fragments of TDP-43 (TDP-43CTD), which are formed upon proteolytic cleavage of fulllength TDP-43 in the nucleus and subsequent transport to the cytoplasm. TDP-43CTD is also known to form stress granules (SGs) by coacervating with RNA in cytoplasm under stress conditions and are believed to be involved in modulating the pathologies. Among other factors affecting these pathologies, the pleiotropic protein called progranulin (PGRN) has gained significant attention lately. The haploinsufficiency of PGRN, caused by autosomal dominant mutations in GRN gene, results in its loss-of-function linked to FTLD and ALS. But precisely how the protein contributes to the pathology remains unknown. Recently, cleavage to GRNs were observed to be a significant part of FTLD and ALS progression with specific GRNs exacerbating TDP-43-induced toxicity in C.elegans. In this report, we show that GRNs -3 and -5 directly interact with TDP-43CTD to modulate latter's aggregation or stress granule formation in disparate ways in vitro. These results constitute the first observation of direct interaction between GRNs and TDP-43 and suggest a mechanism by which the loss of PGRN function could lead to FTLD and ALS.

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Numerous interactions act redundantly to assemble a tunable size of P bodies in Saccharomyces cerevisiae

Cited by 89 publications

References 43 publications

A quantitative inventory of yeast P body proteins reveals principles of composition and specificity

A quantitative inventory of yeast P body proteins reveals principles of composition and specificity

PSP2, a gene encoding RGG-motif protein, is a novel suppressor of clathrin heavy chain deficiency

Granulins modulate liquid-liquid phase separation and aggregation of TDP-43 C-terminal domain

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