Radiation Sensitivity of Esophageal Adenocarcinoma: The Contribution of the RNA-Binding Protein RNPC1 and p21-Mediated Cell Cycle Arrest to Radioresistance

2012 ◽  
Vol 177 (3) ◽  
pp. 272-279 ◽  
Author(s):  
Gijsbert J. Hötte ◽  
Niamh Linam-Lennon ◽  
John V. Reynolds ◽  
Stephen G. Maher
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Esophageal Adenocarcinoma ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Radiation Sensitivity ◽  
Cycle Arrest

scholarly journals The RNA-binding protein SART3 promotes miR-34a biogenesis and G1 cell cycle arrest in lung cancer cells

2019 ◽  
Vol 294 (46) ◽  
pp. 17188-17196 ◽  
Author(s):  
Emily J. Sherman ◽  
Dylan C. Mitchell ◽  
Amanda L. Garner
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mirna Biogenesis ◽  
Regulatory Pathways ◽  
Cycle Arrest

MicroRNAs (miRNAs or miRs) are small, noncoding RNAs that are implicated in the regulation of most biological processes. Global miRNA biogenesis is altered in many cancers, and RNA-binding proteins play a role in miRNA biogenesis, presenting a promising avenue for targeting miRNA dysregulation in diseases. miR-34a exhibits tumor-suppressive activities by targeting cell cycle regulators CDK4/6 and anti-apoptotic factor BCL-2, among other regulatory pathways such as Wnt, TGF-β, and Notch signaling. Many cancers exhibit down-regulation or loss of miR-34a, and synthetic miR-34a supplementation has been shown to inhibit tumor growth in vivo. However, the post-transcriptional mechanisms that cause miR-34a loss in cancer are not entirely understood. Here, using a proteomics-mediated approach in non-small-cell lung cancer (NSCLC) cells, we identified squamous cell carcinoma antigen recognized by T-cells 3 (SART3) as a putative pre-miR-34a–binding protein. SART3 is a spliceosome recycling factor and nuclear RNA-binding protein with no previously reported role in miRNA regulation. We found that SART3 binds pre-miR-34a with higher specificity than pre-let-7d (used as a negative control) and elucidated a new functional role for SART3 in NSCLC cells. SART3 overexpression increased miR-34a levels, down-regulated the miR-34a target genes CDK4/6, and caused a cell cycle arrest in the G1 phase. In vitro binding experiments revealed that the RNA-recognition motifs within the SART3 sequence are responsible for selective pre-miR-34a binding. Our results provide evidence for a significant role of SART3 in miR-34a biogenesis and cell cycle progression in NSCLC cells.

scholarly journals MCG10, a Novel p53 Target Gene That Encodes a KH Domain RNA-Binding Protein, Is Capable of Inducing Apoptosis and Cell Cycle Arrest in G2-M

2000 ◽  
Vol 20 (15) ◽  
pp. 5602-5618 ◽  
Author(s):  
Jianhui Zhu ◽  
Xinbin Chen
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Target Gene ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Wild Type ◽  
Cycle Arrest ◽  
Kh Domain ◽  
P53 Target Gene

ABSTRACT p53, a tumor suppressor, inhibits cell proliferation by inducing cellular genes involved in the regulation of the cell cycle.MCG10, a novel cellular p53 target gene, was identified in a cDNA subtraction assay with mRNA isolated from a p53-producing cell line. MCG10 can be induced by wild-type but not mutant p53 and by DNA damage via two potential p53-responsive elements in the promoter of the MCG10 gene. The MCG10 gene contains 10 exons and is located at chromosome 3p21, a region highly susceptible to aberrant chromosomal rearrangements and deletions in human neoplasia. The MCG10 gene locus encodes at least two alternatively spliced transcripts, MCG10 and MCG10as. The MCG10 and MCG10as proteins contain two domains homologous to the heterogeneous nuclear ribonucleoprotein K homology (KH) domain. By generating cell lines that inducibly express either wild-type or mutated forms of MCG10 and MCG10as, we found that MCG10 and MCG10as can suppress cell proliferation by inducing apoptosis and cell cycle arrest in G2-M. In addition, we found that MCG10 and MCG10as, through their KH domains, can bind poly(C) and that their RNA-binding activity is necessary for inducing apoptosis and cell cycle arrest. Furthermore, we found that the level of the poly(C) binding MCG10 protein is increased in cells treated with the DNA-damaging agent camptothecin in a p53-dependent manner. These results suggest that the MCG10 RNA-binding protein is a potential mediator of p53 tumor suppression.

scholarly journals The TIA1 RNA-Binding Protein Family Regulates EIF2AK2-Mediated Stress Response and Cell Cycle Progression

2018 ◽  
Vol 69 (4) ◽  
pp. 622-635.e6 ◽  
Author(s):  
Cindy Meyer ◽  
Aitor Garzia ◽  
Michael Mazzola ◽  
Stefanie Gerstberger ◽  
Henrik Molina ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stress Response ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Family ◽  
Cycle Progression

scholarly journals A Novel Role for the RNA–Binding Protein FXR1P in Myoblasts Cell-Cycle Progression by Modulating p21/Cdkn1a/Cip1/Waf1 mRNA Stability

PLoS Genetics ◽  
2013 ◽  
Vol 9 (3) ◽  
pp. e1003367 ◽  
Author(s):  
Laetitia Davidovic ◽  
Nelly Durand ◽  
Olfa Khalfallah ◽  
Ricardo Tabet ◽  
Pascal Barbry ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mrna Stability ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cycle Progression

Phosphorylation of RNA-binding protein controls cell cycle switch from mitotic to meiotic in fission yeast

Nature ◽  
1997 ◽  
Vol 386 (6621) ◽  
pp. 187-190 ◽  
Author(s):  
Yoshinori Watanabe ◽  
Satoko Shinozaki-Yabana ◽  
Yuji Chikashige ◽  
Yasushi Hiraoka ◽  
Masayuki Yamamoto
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals Phosphoregulation provides specificity to biomolecular condensates in the cell cycle and cell polarity

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Therese M. Gerbich ◽  
Grace A. McLaughlin ◽  
Katelyn Cassidy ◽  
Scott Gerber ◽  
David Adalsteinsson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nucleic Acids ◽  
Cell Polarity ◽  
Filamentous Fungus ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Ashbya Gossypii ◽  
Mrna Targets ◽  
Functional Identities

Biomolecular condensation is a way of organizing cytosol in which proteins and nucleic acids coassemble into compartments. In the multinucleate filamentous fungus Ashbya gossypii, the RNA-binding protein Whi3 regulates the cell cycle and cell polarity through forming macromolecular structures that behave like condensates. Whi3 has distinct spatial localizations and mRNA targets, making it a powerful model for how, when, and where specific identities are established for condensates. We identified residues on Whi3 that are differentially phosphorylated under specific conditions and generated mutants that ablate this regulation. This yielded separation of function alleles that were functional for either cell polarity or nuclear cycling but not both. This study shows that phosphorylation of individual residues on molecules in biomolecular condensates can provide specificity that gives rise to distinct functional identities in the same cell.

scholarly journals RPSAP52 lncRNA Inhibits p21Waf1/CIP Expression by Interacting With the RNA Binding Protein HuR

2020 ◽  
Vol 28 (2) ◽  
pp. 191-201
Author(s):  
Daniela D’Angelo ◽  
Claudio Arra ◽  
Alfredo Fusco
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenomas ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Kinase Inhibitor ◽  
Cell Transformation ◽  
Binding Protein ◽  
Critical Role ◽  
Rna Binding Protein ◽  
Messenger Rnas

Long noncoding RNAs have been recently demonstrated to have an important role in fundamental biological processes, and their deregulated expression has been found in several human neoplasias. Our group has recently reported a drastic overexpression of the long noncoding RNA (lncRNA) RPSAP52 (ribosomal protein SA pseudogene 52) in pituitary adenomas. We have shown that this lncRNA increased cell proliferation by upregulating the expression of the chromatinic proteins HMGA1 and HMGA2, functioning as a competing endogenous RNA (ceRNA) through competitively binding to microRNA-15a (miR-15a), miR-15b, and miR-16. The aim of this work was to identify further mechanisms by which RPSAP52 overexpression could contribute to the development of pituitary adenomas. We investigated the involvement of RPSAP52 in the modulation of the expression of cell cycle-related genes, such as p21Waf1/CIP, whose deregulation plays a critical role in pituitary cell transformation. We report that RPSAP52, interacting with the RNA binding protein HuR (human antigen R), favors the delocalization of miR-15a, miR-15b, and miR-16 on the cyclin-dependent kinase inhibitor p21Waf1/CIP1 that, accordingly, results in downregulation in pituitary adenomas. A RNA immunoprecipitation sequencing (RIPseq) analysis performed on cells overexpressing RPSAP52 identified 40 messenger RNAs (mRNAs) enriched in Argonaute 2 (AGO2) immunoprecipitated samples. Among them, we focused on GAS8 (growth arrest-specific protein 8) gene. Consistently, GAS8 expression was downregulated in all the analyzed pituitary adenomas with respect to normal pituitary and in RPSAP52-overepressing cells, supporting the role of RPSAP52 in addressing genes involved in growth inhibition and cell cycle arrest to miRNA-induced degradation. This study unveils another RPSAP52-mediated molecular mechanism in pituitary tumorigenesis.

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