Tdrd3 is a novel stress granule-associated protein interacting with the Fragile-X syndrome protein FMRP

Linder, Bastian; Plöttner, Oliver; Kroiß, Matthias; Hartmann, Enno; Laggerbauer, Bernhard; Meister, Gunter; Keidel, Eva; Fischer, Utz

doi:10.1093/hmg/ddn219

Cited by 81 publications

(105 citation statements)

References 39 publications

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“…The human fragile X mental retardation proteins FMRP and FXR1 localize to mammalian SGs (Mazroui et al 2002;Linder et al 2008). We assessed the localization of the Drosophila homolog FMR1 in stressed cells, and found that FMR1 and poly(A) + RNA are co-localized in cytoplasmic granules after exposure to arsenite or 40°C heat shock ( Fig.…”

Section: Drosophila Stress-induced Poly(a)mentioning

confidence: 99%

Metazoan stress granule assembly is mediated by P-eIF2α-dependent and -independent mechanisms

Farny

Kedersha²,

Silver³

2009

RNA

119

110

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Stress granules (SGs) are cytoplasmic bodies wherein translationally silenced mRNAs are recruited for triage in response to environmental stress. We report that Drosophila cells form SGs in response to arsenite and heat shock. Drosophila SGs, like mammalian SGs, are distinct from but adjacent to processing bodies (PBs, sites of mRNA silencing and decay), require polysome disassembly, and are in dynamic equilibrium with polysomes. We further examine the role of the two Drosophila eIF2a kinases, PEK and GCN2, in regulating SG formation in response to heat and arsenite stress. While arsenite-induced SGs are dependent upon eIF2a phosphorylation, primarily via PEK, heat-induced SGs are phospho-eIF2a-independent. In contrast, heat-induced SGs require eIF2a phosphorylation in mammalian cells, as non-phosphorylatable eIF2a Ser51Ala mutant murine embryonic fibroblasts do not form SGs even after severe heat shock. These results suggest that mammals evolved alternative mechanisms for dealing with thermal stress.

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Section: Drosophila Stress-induced Poly(a)mentioning

confidence: 99%

Metazoan stress granule assembly is mediated by P-eIF2α-dependent and -independent mechanisms

Farny

Kedersha²,

Silver³

2009

RNA

119

110

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“…Mutations in MSH5 (Signals #15a and #15b) have been associated with various human diseases including POI 13 . In addition, TDRD3 (Signal #28) is a primary binding partner of FMR1 in which triplet repeat premutations are a risk factor for POI 14 .…”

Section: Anm Snps Enriched In Known Poi Genesmentioning

confidence: 99%

Large-Scale Genomic Analyses Link Reproductive Aging to Hypothalamic Signaling, Breast Cancer Susceptibility, and BRCA1-Mediated DNA Repair

Day

Ruth

Thompson

et al. 2015

Obstetrical &Amp; Gynecological Survey

101

214

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Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ~7 0,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two harbouring additional rare missense alleles of large effect. We found enrichment of signals in/near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses revealed a major association with DNA damageresponse (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomisation analyses supported a causal effect of later ANM on breast cancer risk (~6% risk increase per-year, P=3×10 −14 ), likely mediated by prolonged sex hormone exposure, rather than DDR mechanisms.

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“…Western blot analyses were performed as described previously (Otter et al 2007), using appropriate antibodies. Immunocytochemistry and stress treatment were carried out as depicted in Linder et al (2008).…”

Section: Immunological Proceduresmentioning

confidence: 99%

A stimulatory role for the La-related protein 4B in translation

Schäffler

Schulz²,

Hirmer³

et al. 2010

RNA

Self Cite

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La-related proteins (LARPs) belong to an evolutionarily conserved family of factors with predicted roles in RNA metabolism. Here, we have analyzed the cellular interactions and function of LARP4B, a thus far uncharacterized member of the LARP family. We show that LARP4B is a cytosolic protein that accumulates upon arsenite treatment in cellular stress granules. Biochemical experiments further uncovered an interaction of LARP4B with the cytosolic poly(A) binding protein 1 (PABPC1) and the receptor for activated C Kinase (RACK1), a component of the 40S ribosomal subunit. Under physiological conditions, LARP4B co-sedimented with polysomes in cellular extracts, suggesting a role in translation. In agreement with this notion, overexpression of LARP4B stimulated protein synthesis, whereas knockdown of the factor by RNA interference impaired translation of a large number of cellular mRNAs. In sum, we identified LARP4B as a stimulatory factor of translation. We speculate that LARP4B exerts its function by bridging mRNA factors of the 39 end with initiating ribosomes.

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Tdrd3 is a novel stress granule-associated protein interacting with the Fragile-X syndrome protein FMRP

Cited by 81 publications

References 39 publications

Metazoan stress granule assembly is mediated by P-eIF2α-dependent and -independent mechanisms

Metazoan stress granule assembly is mediated by P-eIF2α-dependent and -independent mechanisms

Large-Scale Genomic Analyses Link Reproductive Aging to Hypothalamic Signaling, Breast Cancer Susceptibility, and BRCA1-Mediated DNA Repair

A stimulatory role for the La-related protein 4B in translation

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