The recently proposed exozyme hypothesis posits that subunits of the RNA processing exosome assemble into structurally distinct protein complexes that function in disparate cellular compartments and RNA metabolic pathways. Here, in a genetic test of this hypothesis, we examine the role of Dis3 -- an essential polypeptide with endo- and 3'' to 5'' exo-ribonuclease activity -- in cell cycle progression. We present several lines of evidence that perturbation of DIS3 affects microtubule (MT) localization and structure in Saccharomyces cerevisiae. Cells with a DIS3 mutation: (i) accumulate anaphase and pre-anaphase mitotic spindles; (ii) exhibit spindles that are mis-oriented and displaced from the bud neck; (iii) harbor elongated spindle-associated astral MTs; (iv) have an increased G1 astral MT length and number; and (v) are hypersensitive to MT poisons. Mutations in the core exosome genes RRP4 and MTR3 and the exosome cofactor gene MTR4 -- but not other exosome subunit gene mutants -- also elicit MT phenotypes. RNA deep sequencing analysis (RNA-seq) shows broad changes in the levels of cell cycle- and microtubule-related transcripts in mutant strains. Collectively, the different mitotic phenotypes and distinct sets of mRNAs affected by the exosome subunit and cofactor mutants studied here suggest that Dis3 has a core exosome-independent role(s) in cell cycle progression. These observations are consistent with the predictions of the exozyme hypothesis and also suggest an evolutionarily conserved role for Dis3 in linking RNA metabolism, MTs, and mitotic progression. Overall design: RNA-seq analysis of total RNA harvested from WT, mtr3-1, mtr4-1, and Dis3^mtr (rrp44-1/mtr17-1) Saccharomyces cerevisiae strains after a temperature shift.
Pronounced and extensive microtubule defects in a Saccharomyces cerevisiae DIS3 mutant.
Cell line, Treatment, Subject
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Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.
Specimen part
View SamplesWe obtained peripheral blood samples for women from Utah (USA) and Ontario (Canada) who had a family history of breast cancer (or did not), who carried a BRCA1/2 mutation (or did not), and who had developed breast cancer (or had not).
Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.
Specimen part
View SamplesWe obtained peripheral blood samples for women from Utah (USA) and Ontario (Canada) who had a family history of breast cancer (or did not), who carried a BRCA1/2 mutation (or did not), and who had developed breast cancer (or had not).
Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility.
Specimen part
View SamplesSenescence can be transmitted in a paracrine way from cells undergoing Oncogene Induced Senescence (OIS) to nave normal cells. We define this phenomenon as paracrine senescence
A complex secretory program orchestrated by the inflammasome controls paracrine senescence.
Specimen part, Cell line
View SamplesThe goal of this study is to understand the alterations in transcriptome induced by histone H3K36M mutations Overall design: Transcritome profiling of 3 cell lines cultured in vitro and 6 murine tumors
Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape.
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View SamplesMaternal obesity during the pre-implantation period leads to a pro-inflammatory milieu in the ovaries. We conducted a global transcriptomic profiling in ovaries from TEN fed rats during the pre-implantation period. Microarray analysis revealed that obesity lead to increased expression of genes related to inflammation, decreased glucose transporters, and dysregulation of ovarian function-related genes in the ovaries. Our results suggest maternal obesity led to an up-regulation of inflammatory genes and Egr-1 protien expression in peri-implantation ovarian tissue, and a concurrent down-regulation of glucose transporters mRNA and AKT and PI3K protein levels.
Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1.
Sex, Specimen part
View SamplesTime-series analysis of response to ribosome 28s damage at gene expression level
Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling.
Cell line, Treatment
View SamplesCUGBP1 and MBNL1 are developmentally regulated RNA-binding proteins that are causally associated with myotonic dystrophy type 1. Using HITS-CLIP anlysis, we found CUGBP1 and MBNL1 preferentially bind to alternatively spliced introns and exons, as well as to the 3' UTRs.
CUGBP1 and MBNL1 preferentially bind to 3' UTRs and facilitate mRNA decay.
Specimen part, Cell line
View SamplesMaternal obesity during pregnancy leads to a pro-inflammatory milieu in the placenta. We conducted a global transcriptomic profiling in BeWo cells following palmitic acid (PA, 500 uM) and/or TNF-alpha (10 ng/ml) treatment for 24 h. Microarray analysis revealed that placental cytotrophoblasts increased expression of genes related to inflammation, stress response and immediate-early factors in response to plamitic acid, TNF-alpha or a combination of both. Our results suggest that fatty acids and inflammatory cytokines induce inflammation in placental cells via activation of JNK-Egr-1 signaling.
Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity.
Specimen part, Cell line
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