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"Abstract Ribosome biogenesis and protein synthesis are dysregulated in several cancers, with those influenced by elevated Pol Iu2013-mediated ribosomal rDNA transcription and mTORC1/eIF4E-driven mRNA translation in some cancers. Here, we show that coordinated targeting of rDNA transcription and PI3K's T1-dependent ribosome biogenesis and protein synthesis results in a dramatic rise in survival in MYC-driven B lymphoma. Eu03bc-Myc lymphoma mice in combination with an RNA transcription blocker and the mTORC1 inhibitor everolimus more than doubled survival of Eu2013bearing mice. The ability of each agent to induce tumor cell death by independent pathways was crucial to their synergistic effectiveness. CX-5461 induced nucleolar stress and P53 pathway activation, while Everolimus induced the expression of the proapoptotic protein BMF that was unintended of p53 and reduced expression of RPL11 and RPL5. MYC's high proportion of cancers causing by MYC's are extremely limited, with no treatment options available. ".
Source link: https://doi.org/10.1158/2159-8290.cd-14-0673
"5u2032-Capping is the first mRNA gene expression change that has measurable consequences for downstream events in gene expression. " Mouse cDNA initiated the synthesis of a 68-kDa polypeptide that also contained RNA 5u2032-triphosphatase activity and catalyzed the production of RNA 5u2032-terminal GpG. The mouse cDNA complemented a haploid strain of Saccharomyces cerevisiae lacking mRNA defoggerase for growth. The results report show that the phosphorylated C-terminal domain of RNA polymerase II couples capping to transcription elongation. These results also discuss the selective capping of RNA polymerase II transcripts. ".
Source link: https://doi.org/10.1073/pnas.94.24.12898
"Abstract Alternative splicing of mRNA precursors allows one gene to produce multiple protein isoforms with differing functions. " We're here to discuss aspects of alternative splicing misregulation in cancer, including deregulation of regulatory splicing techniques and finding mutated components of the splicing machinery. According to new research, changes in gene expressions of regulatory splicing factors and mutations in components of the core splicing machinery have been shown to contribute to misregulation of mRNA splicing in cancer. ".
Source link: https://doi.org/10.1158/2159-8290.cd-13-0253
"Abstract Identifying master regulators that promote pathological gene expression is a significant obstacle in precision oncology. The RNA-binding protein RBMS1 was found to be a suppressor of colon cancer formation in clinical samples, patient-derived xenografts, and cell line models of colon cancer metastasis. We found that silencing RBMS1 results in increased metastatic capacity in xenograft mouse models, and that restoring its expression decreases metastatic liver colonization. Our results indicate that RBMS1 is a previously unknown regulator of RNA stability and as a source of colon cancer metastasis with clinical value for risk stratification of patients. Significance: We've found RBMS1 as a suppressor of metastasis and as a post-transcriptional regulator of RNA stability by applying a new analytic approach to transcriptomic data from clinical samples and models of colon cancer progression using a new analytic strategy.
Source link: https://doi.org/10.1158/2159-8290.cd-19-1375
"We've identified and molecularly characterized a human protein with a M r of 40,880 Dalton. " In both the cytoplasm and the nucleus, as well as in the nuclear envelope, mrnp 41 was shown by cell fragmentation and immunoblotting, particularly in the nuclear envelope. Double immunofluorescence with antibodies against mrnp 41 and the cytoplasmic poly binding protein revealed colocalization to the cytoplasmic meshwork, according to the cytoplasmic meshwork. Those results indicate that mrnp 41 may play a role in nuclear export of mRNPs and/or in cytoplasmic transport on, or attachment to, the cytoskeleton. Mutations in mrnp 41 in Schizosaccharomyces pombe, coded Rae1p, or in Saccharomyces cerevisiae, coded Gle2p, result in mRNA accumulation in the nucleus, although it is unknown if these homologs are mRNA binding proteins as well.
Source link: https://doi.org/10.1073/pnas.94.17.9119
"In amphibian oocytes, an RNA transscribed from the antisense strand of the FGF-2 gene has been implicated in the regulation of FGF-2 mRNA stability. " The FGF-AS protein is found in a large variety of non-CNS tissues in the postnatal period, according to a Western blot analysis with antibodies against the deduced peptide sequence. In the vicinity of the proximal and distal polyadenylation sites, the FGF-AS is correlated to two closely related regions in the developing brain's long 3'u2032 untranslated region of the FGF-2 mRNA, suggesting a role for the antisense RNA in posttranscriptional control of FGF-2 expression in this tissue. The FGF-2 and fgf-as RNAs are coordinately transcribed on a tissue-specific and developmentally controlled basis, according to these results, and they show that interaction of the sense and amorphous RNAs could result in posttranscriptional control of FGF-2 in some tissues.
Source link: https://doi.org/10.1073/pnas.94.10.4943
"In a solution binding assay, recombinant nuclear mRNA-binding protein A1 is directly bound to recombinant nuclear mRNA-binding protein A1. Several nucleoporins with distinctive peptide repeat motifs were linked to a number of karyopherin u03b21, karyopherin u03b21, karyopherin u03b21, ukaryopherin u03b22, and several nucleoporins containing specific peptide repeat motifs as previously reported. Both u03b21 and u03b22 competed with each other for binding to an immobilized repeat nucleoporin Nup98 in a solution that tied assay. U03b22 was able to dock A1 at the nuclear rim and import it into the nucleoplasm, thanks to digitonin-permeabilized cells. Import was stymied by a non-hydrolyzable GTP analog, a Ran mutant that is unable to hydrolyze GTP and by wheat germ agglutinin. u03b21-mediated import of a classical NLS-containing substrate and, vice versa, u03b21-mediated import of A1 substrate and, vice versa, prevented u03b21-mediated import of a classical NLS-containing substrate, indicating that the two import pathways merge at the level of docking of u03b21 and u03b22 to repeat nucleoporins.
Source link: https://doi.org/10.1073/pnas.94.10.5055
"Gene expression analysis requires accurate measurements of global RNA degradation rates, which was earlier incompatible with cell physiology techniques. " Recent, metabolic RNA labeling emerged as an effective and minimally invasive method used in mammalian cells. Here, we have modified SH-linked alkylation for the metabolic sequencing of RNA for a global mRNA stability study in yeast using 4-thiouracil pulse-chase labeling. Instead of steady-state RNA level changes, we then used our yeast protocol to identify targets of the nonsense-mediated decay pathway by monitoring the change in RNA half-lives. We discover 225 novel targets and find a good correlation with recent NMD targets, with 61. 2% of our candidates being identified in previous studies. "Our yeast cultivation developed global quantitative measures of the NMD effect on transcript half-lives, high correlation with RNA half-lives, and the identification of novel NMD controlled transcripts that had not previously reported. ".
Source link: https://doi.org/10.1261/rna.079077.121
"e24072 Background: In phase 3 studies that did not include cancer patients, SARS-CoV-2 vaccines' efficacy and safety were tested. " Methods: The aim of this study is to determine the safety profile of the mRNA-1273 vaccine among cancer patients and its relationship to patient demographics in u2019. Patients 18-years or older with solid malignancies receiving medical care in Hospital Clu00ednico San Carlos who had obtained the mRNA9 1273 vaccine on a three-dose regimen were included in this cross sectional review. The majority of patients had ECOG 0; 38 percent and 8% of the population had ECOG 1 and 2 respectively, while 38 percent and 8 percent of the population had ECOG 1. Local adverse reactions at the site of injection and systemic adverse reactions remained consistent after the first and second doses were more prevalent after the first and second dose than after the third, while systemic adverse reactions were less prevalent after the first and second doses than after the third. After the third dose of a moderate correlation tested by Cramer-u2019s V. Cochran-Armitage test showed a statistically significant linear trend, p = 0. 012, with a smaller proportion of patients suffering from systemic side effects. Females had 5. 79 times higher risks of experiencing systemic adverse events after the third dose compared to males in a logistic regression analysis. To elucidate the safety profile of COVID-19 vaccines in cancer patients, further research is required. ".
Source link: https://doi.org/10.1200/jco.2022.40.16_suppl.e24072
"Anti-syndrome coronavirus type 2 vaccine is especially useful in reducing COVID-19 morbidity and mortality. " By longitudinal serological analysis of SARS-COV-2 spike-binding IgG antibodies, the aim of this study was to determine immunization in TET pts who received two doses of mRNA vaccine. Both research participants received two doses of COVID-19 mRNA vaccine. IgG antibody serological profiles were determined by centralized chemiluminescent immunoassay at various time points, including before 1 st vaccine dose and 1 month after second dose. In 19 TET pts, 19 pts had Goodu2019s Syndrome and ten other immune disorders. At T2, Ab test results were available for 37 pts, while 19 did not achieve seroconversion, according to Ab titers. Conclusions: Our results indicated that TET pts with ED had a significantly higher risk of delayed seroconversion after SARS-COV-2 vaccine than with NED pts.
Source link: https://doi.org/10.1200/jco.2022.40.16_suppl.8588
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