The long noncoding RNA ASNR suppresses Bcl-2 mRNA degradation in apoptosis through affecting nuclei-cytoplasmic transportation of AUF1
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE74568 | GEO | 2015/11/15
SECONDARY ACCESSION(S): PRJNA300848
REPOSITORIES: GEO
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Project description:BackgroundThere exists abundant molecular and ultra-structural evidence to suggest that cytoplasmic actin can physically interact with the nuclear envelope (NE) membrane system. However, this interaction has yet to be characterised in living interphase cells.ResultsUsing a fluorescent conjugate of the actin binding drug cytochalasin D (CD-BODIPY) we provide evidence that polymerising actin accumulates in vicinity to the NE. In addition, both transiently expressed fluorescent actin and cytoplasmic micro-injection of fluorescent actin resulted in accumulation of actin at the NE-membrane. Consistent with the idea that the cytoplasmic phase of NE-membranes can support this novel pool of perinuclear actin polymerisation we show that isolated, intact, differentiated primary hepatocyte nuclei support actin polymerisation in vitro. Further this phenomenon was inhibited by treatments hindering steric access to outer-nuclear-membrane proteins (e.g. wheat germ agglutinin, anti-nesprin and anti-nucleoporin antibodies).ConclusionWe conclude that actin polymerisation occurs around interphase nuclei of living cells at the cytoplasmic phase of NE-membranes.
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Project description:The identification and characterization of long non-coding RNAs (lncRNAs) in diverse biological processes has recently developed rapidly. The large amounts of non-coding RNAs scale consistent with developmental complexity in eukaryotes, indicating that most of these transcripts may have functions in the regulation of biological processes and disorder in the organisms. In particular, Understanding of the overall biological significance of lncRNAs in cancers still remains limited. Here, we found a nuclear-retained lncRNA, termed Lnc_ASNR (apoptosis suppressing-noncoding RNA), which serves as a repressor of apoptosis. Lnc_ASNR was discovered in a set of microarray data derived from four kinds of tumor and adjacent normal tissue samples, and displayed significant up-regulation in the tumor tissues. Using an RNA-pull down assay, we found that Lnc_ASNR interacted with the protein ARE/poly (U)-binding/degradation factor 1(AUF1), which is reported to promote rapid degradation of the Bcl-2 mRNA, an inhibitor of apoptosis. Lnc_ASNR binds to AUFI in nucleus, decreasing the cytoplasmic proportion of AUF1 which targets the B-cell lymphoma-2 (Bcl-2) mRNA. Taken together, the overall effect of Lnc_ASNR expression is thus a decrease in cell apoptosis indicating that Lnc_ASNR may play a vital role in tumorigenesis and carcinogenesis.
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Project description:We used confocal microscopy to evaluate nuclear dynamics in mature, growing hyphae of Neurospora crassa whose nuclei expressed histone H1-tagged green fluorescent protein (GFP). In addition to the H1-GFP wild-type (WT) strain, we examined nuclear displacement (passive transport) in four mutants deficient in microtubule-related motor proteins (ro-1, ro-3, kin-1, and a ro-1 kin-1 double mutant). We also treated the WT strain with benomyl and cytochalasin A to disrupt microtubules and actin microfilaments, respectively. We found that the degree of nuclear displacement in the subapical regions of all strains correlated with hyphal elongation rate. The WT strain and that the ro-1 kin-1 double mutant showed the highest correlation between nuclear movement and hyphal elongation. Although most nuclei seemed to move forward passively, presumably carried by the cytoplasmic bulk flow, a small proportion of the movement detected was either retrograde or accelerated anterograde. The absence of a specific microtubule motor in the mutants ro-1, ro-3, or kin-1 did not prevent the anterograde and retrograde migration of nuclei; however, in the ro-1 kin-1 double mutant retrograde migration was absent. In the WT strain, almost all nuclei were elongated, whereas in all other strains a majority of nuclei were nearly spherical. With only one exception, a sizable exclusion zone was maintained between the apex and the leading nucleus. The ro-1 mutant showed the largest nucleus exclusion zone; only the treatment with cytochalasin A abolished the exclusion zone. In conclusion, the movement and distribution of nuclei in mature hyphae appear to be determined by a combination of forces, with cytoplasmic bulk flow being a major determinant. Motor proteins probably play an active role in powering the retrograde or accelerated anterograde migrations of nuclei and may also contribute to passive anterograde displacement by binding nuclei to microtubules.
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Project description:The antiapoptotic Bcl-2 protein is overexpressed in a variety of cancers, particularly leukemias. In some cell types this is the result of enhanced stability of bcl-2 mRNA, which is controlled by elements in its 3'-untranslated region. Nucleolin is one of the proteins that binds to bcl-2 mRNA, thereby increasing its half-life. Here, we examined the site on the bcl-2 3'-untranslated region that is bound by nucleolin as well as the protein binding domains important for bcl-2 mRNA recognition. RNase footprinting and RNA fragment binding assays demonstrated that nucleolin binds to a 40-nucleotide region at the 5' end of the 136-nucleotide bcl-2 AU-rich element (ARE(bcl-2)). The first two RNA binding domains of nucleolin were sufficient for high affinity binding to ARE(bcl-2). In RNA decay assays, ARE(bcl-2) transcripts were protected from exosomal decay by the addition of nucleolin. AUF1 has been shown to recruit the exosome to mRNAs. When MV-4-11 cell extracts were immunodepleted of AUF1, the rate of decay of ARE(bcl-2) transcripts was reduced, indicating that nucleolin and AUF1 have opposing roles in bcl-2 mRNA turnover. When the function of nucleolin in MV-4-11 cells was impaired by treatment with the nucleolin-targeting aptamer AS1411, association of AUF1 with bcl-2 mRNA was increased. This suggests that the degradation of bcl-2 mRNA induced by AS1411 results from both interference with nucleolin protection of bcl-2 mRNA and recruitment of the exosome by AUF1. Based on our findings, we propose a model that illustrates the opposing roles of nucleolin and AUF1 in regulating bcl-2 mRNA stability.
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Project description:To explore long non-coding RNA (lncRNA) associated with radiosensitivity in colorectal carcinoma cell lines, expression profiles of Lovo, RKO and SW480 cell lines with different levels of radiosensitivity were investigated on ArrayStar platform. A probe-remapping strategy was applied to aquire the accurate probe annotation. By comparing expression profiles of cells with exposure to radiation with those of control sample (cells without exposure), a list of lncRNAs associated with radiation response was compiled. GSEA was then performed to explore their biological functions.
2017-03-03 | GSE95606 | GEO
Project description:Colon cancer cell line RKO grown on Matrigel form a luminal-like structure after the transfection of SPARCL1 gene, which may imply the differentiation of the cells. To indentify genes regulated by SPARCL1, we built two stable cell lines: RKO with pLXSN-SPARCL1 plasmid (RKO-SPARCL1) and RKO with pLXSN plasmid (RKO-pLXSN). Then we cultured these two cell lines on both plastic dish and dish cover with a layer of Matrigel. We used microarrays to undentify global gene expression change in RKO cells after the tranfection of SPARCL1. Four samples including RKO-pLXSN cells cultured on plastic, RKO-pLXSN cells cultured on Matrigel, RKO-SPARCL1 cells cultured on plastic and RKO-SPARCL1 cells cultured on Matrigel were trypsinized and collected for RNA extraction and hybridization on Affymetrix microarray U133plus2.0. Supplementary files: * RLvsRP: up and down regulated genes comparing with RKO-SPARCL1(RL) and RKO-pLXSN(RP) cells cultured on plastic * RLMvsRPM: up and down regulated genes comparing with RKO-SPARCL1(RL) and RKO-pLXSN(RP) cells cultured on Matrigel
2011-09-29 | E-GEOD-31440 | biostudies-arrayexpress
Project description:Colon cancer cell line RKO grown on Matrigel form a luminal-like structure after the transfection of SPARCL1 gene, which may imply the differentiation of the cells. To indentify genes regulated by SPARCL1, we built two stable cell lines: RKO with pLXSN-SPARCL1 plasmid (RKO-SPARCL1) and RKO with pLXSN plasmid (RKO-pLXSN). Then we cultured these two cell lines on both plastic dish and dish cover with a layer of Matrigel. We used microarrays to undentify global gene expression change in RKO cells after the tranfection of SPARCL1.
2011-09-30 | GSE31440 | GEO
Project description:The circadian clock is based on a transcriptional feedback loop with an essential time delay before feedback inhibition. Previous work has shown that PERIOD (PER) proteins generate circadian time cues through rhythmic nuclear accumulation of the inhibitor complex and subsequent interaction with the activator complex in the feedback loop. Although this temporal manifestation of the feedback inhibition is the direct consequence of PER's cytoplasmic trafficking before nuclear entry, how this spatial regulation of the pacemaker affects circadian timing has been largely unexplored. Here we show that circadian rhythms, including wake-sleep cycles, are lengthened and severely unstable if the cytoplasmic trafficking of PER is disrupted by any disease condition that leads to increased congestion in the cytoplasm. Furthermore, we found that the time delay and robustness in the circadian clock are seamlessly generated by delayed and collective phosphorylation of PER molecules, followed by synchronous nuclear entry. These results provide clear mechanistic insight into why circadian and sleep disorders arise in such clinical conditions as metabolic and neurodegenerative diseases and aging, in which the cytoplasm is congested.
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Project description:HIPK2, a member of the homeodomain-interacting protein kinase family, is a transcriptional corepressor whose activity inhibits tumor progression and allows tumor cell apoptosis in response to chemotherapy. HIPK2 regulates the function of numerous molecules and its inhibition by siRNA, hypoxia or mutations, strongly favours molecular pathways involved in tumor progression, angiogenesis, invasion and chemoresistance. Hence the identification of novel molecules regulated by HIPK2 may be beneficial for better understanding tumor progression and for evaluating targeted antitumor therapies. By using microarray analysis, derived from HIPK2 overexpression (that mimics HIPK2 activation) in colon cancer RKO cells, we aim at evaluating the HIPK2 modulated gene expression involved in tumor progression.
2011-12-31 | E-GEOD-31089 | biostudies-arrayexpress