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mRNA degradation

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https://www.readbyqxmd.com/read/28931009/ndfip-allows-nedd4-nedd4l-induced-aqp2-ubiquitination-and-degradation
#1
Christiane Trimpert, Daniel Wesche, Theun de Groot, Martha M Pimentel Rodriguez, Victoria Wong, Dennis T M van den Berg, Lydie Cheval, Carolina A Ariza, Alain Doucet, Igor Stagljar, Peter M T Deen
Regulation of our water homeostasis is fine-tuned by dynamic translocation of Aquaporin-2 (AQP2)-bearing vesicles to and from the plasma membrane of renal principal cells. Whereas binding of vasopressin to its type-2 receptor initiates a cAMP-protein kinase A cascade and AQP2 translocation to the apical membrane, this is counteracted by protein kinase C-activating hormones, resulting in ubiquitination-dependent internalization of AQP2. The proteins targeting AQP2 for ubiquitin-mediated degradation are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28930587/prenylcysteine-oxidase-1-a-pro-oxidant-enzyme-of-low-density-lipoproteins
#2
Luis V Herrera-Marcos, Jose M Lou-Bonafonte, Maria V Martinez-Gracia, Carmen Arnal, María A Navarro, Jesus Osada
Elevated levels of low density lipoproteins (LDLs) cause atherosclerotic disease, and proteomic analyses have found that these lipoproteins are endowed with prenylcysteine lyase. This systematic review summarizes current understanding of this enzyme, now known as prenylcysteine oxidase 1 (PCYOX1), which hydrolyzes the thioether bond of prenylcysteines in the final step in the degradation of prenylated proteins, releasing hydrogen peroxide, cysteine and the isoprenoid aldehyde. Despite the high variability of the PCYOX1 gene, no polymorphism has yet been associated with any disease...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28929622/endonuclease-regnase-1-monocyte-chemotactic-protein-1-induced-protein-1-mcpip1-in-controlling-immune-responses-and-beyond
#3
REVIEW
Osamu Takeuchi
The activation of inflammatory cells is controlled at transcriptional and posttranscriptional levels. Posttranscriptional regulation modifies mRNA stability and translation, allowing for elaborate control of proteins required for inflammation, such as proinflammatory cytokines, prostaglandin synthases, cell surface co-stimulatory molecules, and even transcriptional modifiers. Such regulation is important for coordinating the initiation and resolution of inflammation, and is mediated by a set of RNA-binding proteins (RBPs), including Regnase-1, Roquin, Tristetraprolin (TTP), and AU-rich elements/poly(U)-binding/degradation factor 1 (AUF1)...
September 20, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28928276/precursor-microrna-122-inhibits-synthesis-of-insig1-isoform-mrna-by-modulating-polyadenylation-site-usage
#4
Kara L Norman, Tzu-Chun Chen, Gusti Zeiner, Peter Sarnow
The insulin-induced gene 1 protein (Insig1) inhibits the cholesterol biosynthesis pathway by retaining transcription factor SREBP in the endoplasmic reticulum, and by causing the degradation of HMGCR, the rate-limiting enzyme in cholesterol biosynthesis. Liver-specific microRNA miR-122, on the other hand, enhances cholesterol biosynthesis by an unknown mechanism. We have found that Insig1 mRNAs are generated by alternative cleavage and polyadenylation, resulting in specific isoform mRNA species. During high cholesterol abundance, the short 1...
September 19, 2017: RNA
https://www.readbyqxmd.com/read/28928274/the-ubiquitin-ligase-e3-psh1p-is-required-for-proper-segregation-of-both-centromeric-and-two-micron-plasmids-in-saccharomyces-cerevisiae
#5
Meredith B Metzger, Jessica L Scales, Mitchell F Dunklebarger, Allan M Weissman
Protein degradation by the ubiquitin-proteasome system is essential to many processes. We sought to assess its involvement in the turnover of mitochondrial proteins in Saccharomyces cerevisiae We find that deletion of a specific ubiquitin ligase (E3), Psh1p, increases the abundance of a temperature-sensitive mitochondrial protein, mia40-4pHA, when it is expressed from a centromeric plasmid. Deletion of Psh1p unexpectedly elevates the levels of other proteins expressed from centromeric plasmids. Loss of Psh1p does not increase the rate of turn-over of mia40-4pHA, affect total protein synthesis, or increase the protein levels of chromosomal genes...
September 19, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28928205/bola-is-required-for-the-accurate-regulation-of-c-di-gmp-a-central-player-in-biofilm-formation
#6
Ricardo N Moreira, Clémentine Dressaire, Susana Barahona, Lisete Galego, Volkhard Kaever, Urs Jenal, Cecília M Arraiano
The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28924349/autophagy-promotes-degradation-of-polyethyleneimine-alginate-nanoparticles-in-endothelial-progenitor-cells
#7
Guo-Dong Wang, Yu-Zhen Tan, Hai-Jie Wang, Pei Zhou
Polyethyleneimine (PEI)-alginate (Alg) nanoparticle (NP) is a safe and effective vector for delivery of siRNA or DNA. Recent studies suggest that autophagy is related to cytotoxicity of PEI NPs. However, contribution of autophagy to degradation of PEI-Alg NPs remains unknown. CD34(+)VEGFR-3(+) endothelial progenitor cells isolated from rat bone marrow were treated with 25 kDa branched PEI modified by Alg. After treatment with the NPs, morphological changes and distribution of the NPs in the cells were examined with scanning and transmission electron microscopies...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28924102/microrna-483-5p-modulates-the-expression-of-cartilage-related-genes-in-human-chondrocytes-through-down-regulating-tgf-%C3%AE-1-expression
#8
Ronghua Xu, Jiayi Li, Bo Wei, Weiling Huo, Liming Wang
Transforming growth factor-β1 (TGF-β1) has been reported to improve chondrocytes phenotype and function. The expression levels of microRNA-483-5p (miR-483-5p), a potential regulator of TGF-β signaling pathway, were elevated in chondrocytes of patients with osteoarthritis. In this study, we aimed to explore the role of miR-483-5p for the expression of cartilage-related genes in chondrocytes. Human chondrocytes were harvested from femoral condyle and tibial plateau of different donors (n = 10) following amputation due to sarcomas not involving the joint space...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28919859/the-dietary-constituent-falcarindiol-promotes-cholesterol-efflux-from-thp-1-macrophages-by-increasing-abca1-gene-transcription-and-protein-stability
#9
Limei Wang, Veronika Palme, Nicole Schilcher, Angela Ladurner, Elke H Heiss, Herbert Stangl, Rudolf Bauer, Verena M Dirsch, Atanas G Atanasov
We report increased cholesterol efflux from macrophages in the presence of falcarindiol, an important dietary constituent present in commonly used vegetables and medicinal plants. Falcarindiol (3-20 μM) increased cholesterol efflux from THP-1-derived macrophages. Western blot analysis showed an increased protein level of ABCA1 upon falcarindiol exposure. Quantitative real-time PCR revealed that also ABCA1 mRNA level rise with falcarindiol (10 μM) treatment. The effect of falcarindiol on ABCA1 protein as well as mRNA level were counteracted by co-treatment with BADGE, an antagonist of PPARγ...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28919376/microrna-218-5p-as-a-potential-target-for-the-treatment-of-human-osteoarthritis
#10
Jun Lu, Ming-Liang Ji, Xue-Jun Zhang, Pei-Liang Shi, Hao Wu, Chen Wang, Hee-Jeong Im
Emerging evidence suggests that dysregulated microRNAs (miRNAs) play a pivotal role in osteoarthritis (OA), but the role of specific miRNAs remains unclear. Accordingly, we identified OA-associated miRNAs and functional validation of results. Here, we demonstrate that miR-218-5p is significantly upregulated in moderate and severe OA and correlates with scores on a modified Mankin scale. Through gain-of-function and loss-of-function studies, miR-218-5p was shown to significantly affect matrix synthesis gene expression and chondrocyte proliferation and apoptosis...
August 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28918024/antisense-oligonucleotide-mediated-removal-of-the-polyglutamine-repeat-in-spinocerebellar-ataxia-type-3-mice
#11
Lodewijk J A Toonen, Frank Rigo, Haico van Attikum, Willeke M C van Roon-Mom
Spinocerebellar ataxia type 3 (SCA3) is a currently incurable neurodegenerative disorder caused by a CAG triplet expansion in exon 10 of the ATXN3 gene. The resultant expanded polyglutamine stretch in the mutant ataxin-3 protein causes a gain of toxic function, which eventually leads to neurodegeneration. One important function of ataxin-3 is its involvement in the proteasomal protein degradation pathway, and long-term downregulation of the protein may therefore not be desirable. In the current study, we made use of antisense oligonucleotides to mask predicted exonic splicing signals, resulting in exon 10 skipping from ATXN3 pre-mRNA...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917642/efficient-gene-editing-via-non-viral-delivery-of-crispr-cas9-system-using-polymeric-and-hybrid-microcarriers
#12
Alexander S Timin, Albert R Muslimov, Kirill V Lepik, Olga S Epifanovskaya, Alena I Shakirova, Ulrike Mock, Kristoffer Riecken, Maria V Okilova, Vladislav S Sergeev, Boris V Afanasyev, Boris Fehse, Gleb B Sukhorukov
CRISPR-Cas9 is a revolutionary genome-editing technology that has enormous potential for the treatment of genetic diseases. However, the lack of efficient and safe, non-viral delivery systems has hindered its clinical application. Here, we report on the application of polymeric and hybrid microcarriers, made of degradable polymers such as polypeptides and polysaccharides and modified by silica shell, for delivery of all CRISPR-Cas9 components. We found that these microcarriers mediate more efficient transfection than a commercially available liposome-based transfection reagent (>70% vs...
September 13, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28916784/p-body-proteins-regulate-transcriptional-rewiring-to-promote-dna-replication-stress-resistance
#13
Raphael Loll-Krippleber, Grant W Brown
mRNA-processing (P-) bodies are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study we identify the complete complement of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28912364/novel-pathological-role-of-hnrnpa1-heterogeneous-nuclear-ribonucleoprotein-a1-in-vascular-smooth-muscle-cell-function-and-neointima-hyperplasia
#14
Li Zhang, Qishan Chen, Weiwei An, Feng Yang, Eithne Margaret Maguire, Dan Chen, Cheng Zhang, Guanmei Wen, Mei Yang, Bin Dai, Le Anh Luong, Jianhua Zhu, Qingbo Xu, Qingzhong Xiao
OBJECTIVE: hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) plays a variety of roles in gene expression. However, little is known about the functional involvement of hnRNPA1 in vascular smooth muscle cell (VSMC) function and neointima hyperplasia. In this study, we have attempted to investigate the functional roles of hnRNPA1 in the contexts of VSMC function, injury-induced vessel remodeling, and human atherosclerotic lesions, as well as discern the molecular mechanisms involved. APPROACH AND RESULTS: hnRNPA1 expression levels were consistently modulated during VSMC phenotype switching and neointimal lesion formation induced by wire injury...
September 14, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28912036/dual-effects-of-the-pi3k-inhibitor-zstk474-on-multidrug-efflux-pumps-in-resistant-cancer-cells
#15
Divya Muthiah, Richard Callaghan
ZSTK474 is a potent phosphoinositide 3-kinase (PI3K) inhibitor that reduces cell proliferation via G1-arrest. However, there is little information on the susceptibility of this anticancer drug to resistance conferred by the multidrug pumps P-glycoprotein (ABCB1) and ABCG2. We have demonstrated that ZSTK474 generated cytotoxicity in cells over-expressing either pump with potency similar to that in drug sensitive cells. In addition, the co-administration of ZSTK474 with the cytotoxic anti-cancer drugs vinblastine and mitoxantrone caused a potentiated cytotoxic effect in both drug sensitive and efflux pump expressing cells...
September 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28911210/a20-an-essential-component-of-the-ubiquitin-editing-protein-complex-is-a-negative-regulator-of-inflammation-in-human-myometrium-and-foetal-membranes
#16
Martha Lappas
STUDY QUESTION: Does A20 regulate mediators involved in the terminal processes of human labour in primary myometrial and amnion cells? SUMMARY ANSWER: A20 is a nuclear factor-kappa B (NF-κB) responsive gene that acts as a negative regulator of NF-κB-induced expression of pro-labour mediators. WHAT IS KNOWN ALREADY: Inflammation is commonly implicated in spontaneous preterm birth and the processes involved in rupture of foetal membranes and uterine contractions...
September 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28903374/resveratrol-enhances-polyubiquitination-mediated-arv7-degradation-in-prostate-cancer-cells
#17
Sarah Wilson, Lucia Cavero, Dali Tong, Qiuli Liu, Kyla Geary, Nicholas Talamonti, Jing Xu, Junjiang Fu, Jun Jiang, Dianzheng Zhang
Although androgen deprivation therapy (ADT) serves as the primary treatment option for localized or metastatic prostate cancer, most cases eventually develop into castration-resistant prostate cancer (CRPC). However, androgen receptor (AR) continues to be functional in CRPC through various mechanisms, including the development of AR splicing variants, especially ARV7. Since it lacks the ligand binding domain but retains the intact DNA binding domain, ARV7 is constitutively active, which makes ARV7-positive prostate cancer responsive to neither abiraterone nor enzalutamide...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902152/micrornas-as-biomarkers-in-colorectal-cancer
#18
REVIEW
Takaaki Masuda, Naoki Hayashi, Yosuke Kuroda, Shuhei Ito, Hidetoshi Eguchi, Koshi Mimori
MicroRNAs (miRs) are small RNAs that repress mRNA translation, resulting in the degradation of mRNAs and regulation of the expression levels of various genes. Recent studies have shown that aberrant miR expression has a functional role in the initiation and progression of various malignancies, including colorectal cancer (CRC), which is one of the leading causes of cancer-related death worldwide. miRs have also been shown to have applications as diagnostic, prognostic, and predictive biomarkers because of their high tissue specificity, stability, and altered expression in tumor development...
September 13, 2017: Cancers
https://www.readbyqxmd.com/read/28901390/microrna-132-induces-temozolomide-resistance-and-promotes-the-formation-of-cancer-stem-cell-phenotypes-by-targeting-tumor-suppressor-candidate%C3%A2-3-in-glioblastoma
#19
Zhen-Xiu Cheng, Wen-Bo Yin, Zhong-Yu Wang
The prognosis of patients suffering from glioblastoma [also referred to as glioblastoma multiforme (GBM)] is dismal despite multimodal therapy. Chemotherapy with temozolomide may suppress tumor growth for a certain period of time (a few months); however, invariable tumor recurrence suggests that glioblastoma initiating cells (GICs) render these tumors persistant. Thus, the understanding of the molecular mechanisms of action of GICs as regards their role in the progression of GBM is important as such knowledge will be helpful in the discovery of novel drug targets, as well as in the design of novel therapeutic strategies for more effective treatment of the disease...
September 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28899909/depletion-of-the-mrna-translation-initiation-inhibitor-programmed-cell-death-protein-4-pdcd4-impairs-l6-myotube-formation
#20
Naomi Maeda, Abdikarim Abdullahi, Brendan Beatty, Zameer Dhanani, Olasunkanmi A J Adegoke
The mechanistic (mammalian) target of rapamycin complex 1 (mTORC1) signaling is vital for optimal muscle mass and function. Although the significance of mTORC1 in stimulating muscle growth is unequivocal, evidence in support of its role during muscle regeneration is less clear. Here, we showed that the abundance (protein and mRNA) of the mTORC1/S6K1 substrate, programmed cell death protein 4 (PDCD4), is upregulated at the onset of differentiation of L6 and C2C12 cells. The increase in PDCD4 was not associated with any changes in S6K1 activation, but the abundance of beta transducing repeat-containing protein (β-TrCP), the ubiquitin ligase that targets PDCD4 for degradation, increased...
September 2017: Physiological Reports
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