scholarly journals RNA Interference Knockdown of hU2AF35 Impairs Cell Cycle Progression and Modulates Alternative Splicing of Cdc25 Transcripts

2006 ◽  
Vol 17 (10) ◽  
pp. 4187-4199 ◽  
Author(s):  
Teresa Raquel Pacheco ◽  
Luís Ferreira Moita ◽  
Anita Quintal Gomes ◽  
Nir Hacohen ◽  
Maria Carmo-Fonseca
Keyword(s):  
Cell Cycle ◽  
Alternative Splicing ◽  
Rna Interference ◽  
Cell Cycle Progression ◽  
Protein Isoforms ◽  
Cell Cycle Gene ◽  
Mitotic Progression ◽  
Cycle Progression ◽  
Specific Subset ◽  
Alternatively Spliced

U2AF is a heterodimeric splicing factor composed of a large (U2AF65) and a small (U2AF35) subunit. In humans, alternative splicing generates two U2AF35 variants, U2AF35a and U2AF35b. Here, we used RNA interference to specifically ablate the expression of each isoform in HeLa cells. Our results show that knockdown of the major U2AF35a isoform reduced cell viability and impaired mitotic progression, leading to accumulation of cells in prometaphase. Microarray analysis revealed that knockdown of U2AF35a affected the expression level of ∼500 mRNAs, from which >90% were underrepresented relative to the control. Among mRNAs underrepresented in U2AF35a-depleted cells we identified an essential cell cycle gene, Cdc27, for which there was an increase in the ratio between unspliced and spliced RNA and a significant reduction in protein level. Furthermore, we show that depletion of either U2AF35a or U2AF35b altered the ratios of alternatively spliced isoforms of Cdc25B and Cdc25C transcripts. Taken together our results demonstrate that U2AF35a is essential for HeLa cell division and suggest a novel role for both U2AF35 protein isoforms as regulators of alternative splicing of a specific subset of genes.

scholarly journals Heat shock protein 27 promotes cell cycle progression by down-regulating E2F transcription factor 4 and retinoblastoma family protein p130

2018 ◽  
Vol 293 (41) ◽  
pp. 15815-15826 ◽  
Author(s):  
Ah-Mee Park ◽  
Ikuo Tsunoda ◽  
Osamu Yoshie
Keyword(s):  
Cell Cycle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cellular Senescence ◽  
Cell Cycle Progression ◽  
Heat Shock Protein 27 ◽  
Serum Starvation ◽  
Cell Cycle Gene ◽  
Cycle Progression ◽  
Human Lung Fibroblast

Heat shock protein 27 (HSP27) protects cells under stress. Here, we demonstrate that HSP27 also promotes cell cycle progression of MRC-5 human lung fibroblast cells. Serum starvation for 24 h induced G1 arrest in these cells, and upon serum refeeding, the cells initiated cell cycle progression accompanied by an increase in HSP27 protein levels. HSP27 levels peaked at 12 h, and transcriptional up-regulation of six G2/M-related genes (CCNA2, CCNB1, CCNB2, CDC25C, CDCA3, and CDK1) peaked at 24–48 h. siRNA-mediated HSP27 silencing in proliferating MRC-5 cells induced G2 arrest coinciding with down-regulation of these six genes. Of note, the promoters of all of these genes have the cell cycle–dependent element and/or the cell cycle gene-homology region. These promoter regions are known to be bound by the E2F family proteins (E2F-1 to E2F-8) and retinoblastoma (RB) family proteins (RB1, p107, and p130), among which E2F-4 and p130 were strongly up-regulated in HSP27-knockdown cells. E2F-4 or p130 knockdown concomitant with the HSP27 knockdown rescued MRC-5 cells from G2 arrest and up-regulated the six cell cycle genes. Moreover, we observed cellular senescence in MRC-5 cells on day 3 after the HSP27 knockdown, as evidenced by increased senescence-associated β-gal activity and up-regulated inflammatory cytokines. The cellular senescence was also suppressed by the concomitant knockdown of E2F-4/HSP27 or p130/HSP27. Our findings indicate that HSP27 promotes cell cycle progression of MRC-5 cells by suppressing expression of the transcriptional repressors E2F-4 and p130.

Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart

2008 ◽  
Vol 33 (2) ◽  
pp. 148-158 ◽  
Author(s):  
Jing Chen ◽  
Sara A. Carney ◽  
Richard E. Peterson ◽  
Warren Heideman
Keyword(s):  
Heart Failure ◽  
Cell Cycle ◽  
Heart Development ◽  
Cell Cycle Progression ◽  
Transcriptional Response ◽  
Cell Cycle Gene ◽  
Zebrafish Embryos ◽  
Transcriptional Responses ◽  
Cycle Progression ◽  
Necessary And Sufficient

Retinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) activate distinct ligand-dependent transcription factors, and both cause cardiac malformation and heart failure in zebrafish embryos. We hypothesized that they cause this response by hyperactivating a common set of genes critical for heart development. To test this, we used microarrays to measure transcript changes in hearts isolated from zebrafish embryos 1, 2, 4, and 12 h after exposure to 1 μM RA. We used hierarchical clustering to compare the transcriptional responses produced in the embryonic heart by RA and TCDD. We could identify no early responses in common between the two agents. However, at 12 h both treatments produced a dramatic downregulation of a common cluster of cell cycle progression genes, which we term the cell cycle gene cluster. This was associated with a halt in heart growth. These results suggest that RA and TCDD ultimately trigger a common transcriptional response associated with heart failure, but not through the direct activation of a common set of genes. Among the genes rapidly induced by RA was Nr2F5, a member of the COUP-TF family of transcriptional repressors. We found that induction of Nr2F5 was both necessary and sufficient for the cardiotoxic response to RA.

scholarly journals Author response: An extensive program of periodic alternative splicing linked to cell cycle progression

2016 ◽  
Author(s):  
Daniel Dominguez ◽  
Yi-Hsuan Tsai ◽  
Robert Weatheritt ◽  
Yang Wang ◽  
Benjamin J Blencowe ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Alternative Splicing ◽  
Cell Cycle Progression ◽  
Author Response ◽  
Cycle Progression ◽  
Extensive Program

scholarly journals Proper division plane orientation and mitotic progression together allow normal growth of maize

2017 ◽  
Vol 114 (10) ◽  
pp. 2759-2764 ◽  
Author(s):  
Pablo Martinez ◽  
Anding Luo ◽  
Anne Sylvester ◽  
Carolyn G. Rasmussen
Keyword(s):  
Cell Cycle ◽  
Cell Biology ◽  
Cell Cycle Progression ◽  
Normal Growth ◽  
Mitotic Progression ◽  
Wild Type ◽  
Cycle Progression ◽  
Division Plane ◽  
Plane Orientation ◽  
Division Plane Orientation

How growth, microtubule dynamics, and cell-cycle progression are coordinated is one of the unsolved mysteries of cell biology. A maize mutant,tangled1, with known defects in growth and proper division plane orientation, and a recently characterized cell-cycle delay identified by time-lapse imaging, was used to clarify the relationship between growth, cell cycle, and proper division plane orientation. Thetangled1mutant was fully rescued by introduction of cortical division site localized TANGLED1-YFP. A CYCLIN1B destruction box was fused to TANGLED1-YFP to generate a line that mostly rescued the division plane defect but still showed cell-cycle delays when expressed in thetangled1mutant. Although an intermediate growth phenotype between wild-type and thetangled1mutant was expected, these partially rescued plants grew as well as wild-type siblings, indicating that mitotic progression delays alone do not alter overall growth. These data indicate that division plane orientation, together with proper cell-cycle progression, is critical for plant growth.

scholarly journals RB, p130 and p107 differentially repress G1/S and G2/M genes after p53 activation

2019 ◽  
Vol 47 (21) ◽  
pp. 11197-11208 ◽  
Author(s):  
Amy E Schade ◽  
Martin Fischer ◽  
James A DeCaprio
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Human Fibroblasts ◽  
Cell Cycle Gene ◽  
Cycle Progression ◽  
Cell Cycle Genes ◽  
P53 Activation ◽  
S Genes

Abstract Cell cycle gene expression occurs in two waves. The G1/S genes encode factors required for DNA synthesis and the G2/M genes contribute to mitosis. The Retinoblastoma protein (RB) and DREAM complex (DP, RB-like, E2F4 and MuvB) cooperate to repress all cell cycle genes during G1 and inhibit entry into the cell cycle. DNA damage activates p53 leading to increased levels of p21 and inhibition of cell cycle progression. Whether the G1/S and G2/M genes are differentially repressed by RB and the RB-like proteins p130 and p107 in response to DNA damage is not known. We performed gene expression profiling of primary human fibroblasts upon DNA damage and assessed the effects on G1/S and G2/M genes. Upon p53 activation, p130 and RB cooperated to repress the G1/S genes. In addition, in the absence of RB and p130, p107 contributed to repression of G1/S genes. In contrast, G2/M genes were repressed by p130 and p107 after p53 activation. Furthermore, repression of G2/M genes by p107 and p130 led to reduced entry into mitosis. Our data demonstrates specific roles for RB, p130-DREAM, and p107-DREAM in p53 and p21 mediated repression of cell cycle genes.

scholarly journals Characterization of a novel CDC gene (ORC1) partly homologous to CDC6 of Saccharomyces cerevisiae.

1996 ◽  
Vol 7 (3) ◽  
pp. 409-418 ◽  
Author(s):  
Y Hori ◽  
K Shirahige ◽  
C Obuse ◽  
T Tsurimoto ◽  
H Yoshikawa
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Sequence Data ◽  
Cell Cycle Gene ◽  
Computer Search ◽  
Cycle Progression ◽  
Nucleotide Sequence Data ◽  
Haploid Strain ◽  
Cloned Gene

A novel cell cycle gene was identified by a computer search for genes partly homologous to known CDC genes, CDC6 of Saccharomyces cerevisiae and CDC18 of Schizosaccharomyces pombe, using the nucleotide sequence data base for S. cerevisiae produced by the Yeast Sequencing Project. The protein sequence coded by the cloned gene was found to be identical to that of purified ORC1 protein. Disruption of the gene and subsequent tetrad analysis revealed that the gene was essential for growth. The function of the gene product was analyzed by depleting the protein from the cell using a mutant haploid strain containing the disrupted ORC1 gene on the chromosome and a galactose-inducible gene coding for HA-tagged ORC1 protein on a single copy plasmid. The HA-tagged protein was expressed during growth in the presence of galactose but began to decrease rapidly upon depletion of galactose. Analysis of the cell cycle progression of the mutant cells by FACS after the removal of galactose from the medium, and microscope observations of cells and their nuclei revealed that the normal progression of 2N cells was immediately impeded as the ORC1 protein started to decrease. This was blocked completely in the cells that had progressed to the S phase under conditions deficient in ORC1 protein followed by cell death. Two-dimensional gel analysis of the replication intermediates after the galactose removal revealed that the depletion of ORC1 protein caused a decrease in the frequency of initiation of chromosomal replication, eventually resulting in the inhibition of replication as a whole. The function of the ORC1 protein in the cell cycle progression of S. cerevisiae is discussed in light of current information on ORC.

Inhibition of cell cycle progression by the alternatively spliced integrin beta 1C

Science ◽  
1995 ◽  
Vol 269 (5230) ◽  
pp. 1570-1572 ◽  
Author(s):  
J Meredith ◽  
Y Takada ◽  
M Fornaro ◽  
L. Languino ◽  
M. Schwartz
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Alternatively Spliced
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