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https://www.readbyqxmd.com/read/29679667/systemic-delivery-of-bace1-sirna-through-neuron-targeted-nanocomplexes-for-treatment-of-alzheimer-s-disease
#1
Pengzhen Wang, Xiaoyao Zheng, Qian Guo, Peng Yang, Xiaoying Pang, Kang Qian, Wei Lu, Qizhi Zhang, Xinguo Jiang
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme to cleave the amyloid precursor protein to develop Alzheimer's disease (AD). Reducing BACE1 expression in central neuron through RNA interference technology shows great promise to overcome AD. However, to obtain an efficient and neurons-specific delivery of siRNA against BACE1 through systemic administration remains challenging. Here, we design and prepare siRNA nano-carriers based on PEGylated poly(2-(N,N-dimethylamino) ethyl methacrylate) (PEG-PDMAEMA) modified with both the CGN peptide for blood-brain barrier (BBB) penetration and the Tet1 peptide for neuron-specific binding...
April 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29679511/light-availability-impacts-structure-and-function-of-phototrophic-stream-biofilms-across-domains-and-trophic-levels
#2
Mia M Bengtsson, Karoline Wagner, Clarissa Schwab, Tim Urich, Tom J Battin
Phototrophic biofilms are ubiquitous in freshwater and marine environments where they are critical for biogeochemical cycling, food webs and in industrial applications. In streams, phototrophic biofilms dominate benthic microbial life and harbor an immense prokaryotic and eukaryotic microbial biodiversity with biotic interactions across domains and trophic levels. Here, we examine how community structure and function of these biofilms respond to varying light availability, as the crucial energy source for phototrophic biofilms...
April 21, 2018: Molecular Ecology
https://www.readbyqxmd.com/read/29679401/translational-regulation-of-ribosomal-protein-s15-drives-characteristic-patterns-of-protein-mrna-epistasis
#3
Saurav Mallik, Sudipto Basu, Suman Hait, Sudip Kundu
Do coding and regulatory segments of a gene co-evolve with each-other? Seeking answers to this question, here we analyze the case of Escherichia coli ribosomal protein S15, that represses its own translation by specifically binding its messenger RNA (rpsO mRNA) and stabilizing a pseudoknot structure at the upstream untranslated region, thus trapping the ribosome into an incomplete translation initiation complex. In the absence of S15, ribosomal protein S1 recognizes rpsO and promotes translation by melting this very pseudoknot...
April 21, 2018: Proteins
https://www.readbyqxmd.com/read/29679004/the-linc01138-drives-malignancies-via-activating-arginine-methyltransferase-5-in-hepatocellular-carcinoma
#4
Zhe Li, Jiwei Zhang, Xinyang Liu, Shengli Li, Qifeng Wang, Di Chen, Zhixiang Hu, Tao Yu, Jie Ding, Jinjun Li, Ming Yao, Jia Fan, Shenglin Huang, Qiang Gao, Yingjun Zhao, Xianghuo He
Recurrent chromosomal aberrations have led to the discovery of oncogenes or tumour suppressors involved in carcinogenesis. Here we characterized an oncogenic long intergenic non-coding RNA in the frequent DNA-gain regions in hepatocellular carcinoma (HCC), LINC01138 (long intergenic non-coding RNA located on 1q21.2). The LINC01138 locus is frequently amplified in HCC; the LINC01138 transcript is stabilized by insulin like growth factor-2 mRNA-binding proteins 1/3 (IGF2BP1/IGF2BP3) and is associated with the malignant features and poor outcomes of HCC patients...
April 20, 2018: Nature Communications
https://www.readbyqxmd.com/read/29678949/hu-antigen-r-regulates-antiviral-innate-immune-responses-through-the-stabilization-of-mrna-for-polo-like-kinase-2
#5
Takuya Sueyoshi, Takumi Kawasaki, Yuichi Kitai, Daisuke Ori, Shizuo Akira, Taro Kawai
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), RIG-I, and melanoma differentiation-associated gene 5 (MDA5) play a critical role in inducing antiviral innate immune responses by activating IFN regulatory factor 3 (IRF3) and NF-κB, which regulates the transcription of type I IFN and inflammatory cytokines. Antiviral innate immune responses are also regulated by posttranscriptional and translational mechanisms. In this study, we identified an RNA-binding protein HuR as a regulator for RLR signaling...
April 20, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29678883/ribosome-maturation-by-the-endoribonuclease-ybey-stabilises-a-type-iii-secretion-system-transcript-required-for-virulence-of-enterohemorrhagic-escherichia-coli
#6
Sean P McAteer, Brandon M Sy, Julia L Wong, David Tollervey, David L Gally, Jai J Tree
Enterohemorrhagic Escherichia coli (EHEC) is a significant human pathogen that colonizes humans and its reservoir host, cattle. Colonization requires the expression of a type III secretion (T3S) system that injects a cocktail of effector proteins into host cells, to promote bacterial attachment and disease progression. The T3S system is tightly regulated by a complex network of transcriptional and post-transcriptional regulators. Using transposon mutagenesis, here we identified the ybeZYX-int operon as being required for normal T3S levels...
April 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29678826/rna-binding-protein-hur-regulates-scn5a-expression-through-stabilizing-mef2c-transcription-factor-mrna
#7
Anyu Zhou, Guangbin Shi, Gyeoung-Jin Kang, An Xie, Hong Liu, Ning Jiang, Man Liu, Euy-Myoung Jeong, Samuel C Dudley
BACKGROUND: Although transcription is the initial process of gene expression, posttranscriptional gene expression regulation has also played a critical role for fine-tuning gene expression in a fast, precise, and cost-effective manner. Although the regulation of sodium channel α-subunit ( SCN5A ) mRNA expression has been studied at both transcriptional and pre-mRNA splicing levels, the molecular mechanisms governing SCN5A mRNA expression are far from clear. METHODS AND RESULTS: Herein, we show that, as evidenced by ribonucleoprotein immunoprecipitation assay, RNA binding protein Hu antigen R/ELAV like RNA binding protein 1 (HuR/ELAVL1) and myocyte enhancer factor-2C (MEF2C) transcription factor mRNA are associated...
April 20, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29677482/allosteric-ligands-for-the-pharmacologically-important-flavivirus-target-ns5-from-zinc-database-based-on-pharmacophoric-points-free-energy-calculations-and-dynamics-correlation
#8
Abbas Khan, Shoaib Saleem, Muhammad Idrees, Syed Shujait Ali, Muhammad Junaid, Aman Chandra Kaushik, Dong-Qing Wei
Dengue virus belongs to a group of human pathogens, which causes different diseases, dengue hemorrhagic fever and dengue shock syndrome in humans. It possesses RNA as a genetic material and is replicated with the aid of NS5 protein. RNA-dependent RNA polymerase (RdRp) is an important domain of NS5 in the replication of that virus. The catalytic process activity of RdRp is making it an important target for antiviral chemical therapy. To date, No FDA drug has been approved and marketed for the treatment of diseases caused by Dengue virus...
April 11, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29676910/5-phosphorothiolate-dinucleotide-cap-analogs-reagents-for-mrna-modification-and-potent-small-molecular-inhibitors-of-decapping-enzymes
#9
Blazej Andrzej Wojtczak, Pawel J Sikorski, Kaja Fac-Dabrowska, Anna Nowicka, Marcin Warminski, Dorota Kubacka, Elzbieta Nowak, Marcin Nowotny, Joanna Kowalska, Jacek Jemielity
The 5' cap consists of 7-methylguanosine (m7G) linked by a 5'-5'-triphosphate bridge to mRNA and acts as the master regu-lator of mRNA turnover and translation initiation in eukaryotes. Cap analogs that influence mRNA translation and turnover (either as small molecules or as part of an RNA transcript) are valuable tools for studying gene expression, which is often also of therapeutic relevance. Here, we synthesized a series of 15 dinucleotide cap (m7GpppG) analogs containing a 5'-phosphorothiolate (5'-PSL) moiety (i...
April 20, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29676246/enzymes-involved-in-posttranscriptional-rna-metabolism-in-gram-negative-bacteria
#10
Bijoy K Mohanty, Sidney R Kushner
Gene expression in Gram-negative bacteria is regulated at many levels, including transcription initiation, RNA processing, RNA/RNA interactions, mRNA decay, and translational controls involving enzymes that alter translational efficiency. In this review, we discuss the various enzymes that control transcription, translation, and RNA stability through RNA processing and degradation. RNA processing is essential to generate functional RNAs, while degradation helps control the steady-state level of each individual transcript...
April 2018: Microbiology Spectrum
https://www.readbyqxmd.com/read/29672716/mir-122-does-not-impact-recognition-of-the-hcv-genome-by-innate-sensors-of-rna-but-rather-protects-the-5-end-from-the-cellular-pyrophosphatases-dom3z-and-dusp11
#11
Yalena Amador-Cañizares, Annie Bernier, Joyce A Wilson, Selena M Sagan
Hepatitis C virus (HCV) recruits two molecules of the liver-specific microRNA-122 (miR-122) to the 5' end of its genome. This interaction promotes viral RNA accumulation, but the precise mechanism(s) remain incompletely understood. Previous studies suggest that miR-122 is able to protect the HCV genome from 5' exonucleases (Xrn1/2), but this protection is not sufficient to account for the effect of miR-122 on HCV RNA accumulation. Thus, we investigated whether miR-122 was also able to protect the viral genome from innate sensors of RNA or cellular pyrophosphatases...
April 17, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29670832/innovations-in-biomedical-nanoengineering-nanowell-array-biosensor
#12
REVIEW
YoungTae Seo, Sunil Jeong, JuKyung Lee, Hak Soo Choi, Jonghan Kim, HeaYeon Lee
Nanostructured biosensors have pioneered biomedical engineering by providing highly sensitive analyses of biomolecules. The nanowell array (NWA)-based biosensing platform is particularly innovative, where the small size of NWs within the array permits extremely profound sensing of a small quantity of biomolecules. Undoubtedly, the NWA geometry of a gently-sloped vertical wall is critical for selective docking of specific proteins without capillary resistances, and nanoprocessing has contributed to the fabrication of NWA electrodes on gold substrate such as molding process, e-beam lithography, and krypton-fluoride (KrF) stepper semiconductor method...
2018: Nano Convergence
https://www.readbyqxmd.com/read/29669917/ribosomal-dna-copy-loss-and-repeat-instability-in-atrx-mutated-cancers
#13
Maheshi Udugama, Elaine Sanij, Hsiao P J Voon, Jinbae Son, Linda Hii, Jeremy D Henson, F Lyn Chan, Fiona T M Chang, Yumei Liu, Richard B Pearson, Paul Kalitsis, Jeffrey R Mann, Philippe Collas, Ross D Hannan, Lee H Wong
ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors...
April 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29669788/h19-induces-abdominal-aortic-aneurysm-development-and-progression
#14
Daniel Y Li, Albert Busch, Hong Jin, Ekaterina Chernogubova, Jaroslav Pelisek, Joakim Karlsson, Bengt Sennblad, Shengliang Liu, Shen Lao, Patrick Hofmann, Alexandra Bäcklund, Suzanne M Eken, Joy Roy, Per Eriksson, Brian Dacken, Deepak Ramanujam, Anne Dueck, Stefan Engelhardt, Reinier A Boon, Hans-Henning Eckstein, Joshua M Spin, Philip S Tsao, Lars Maegdefessel
Background -Long noncoding RNAs (lncRNAs) have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify and functionally characterize lncRNAs as potential mediators in abdominal aortic aneurysm (AAA) development. Methods -We profiled RNA transcript expression in two murine AAA models, Angiotensin II (ANGII) infusion in ApoE-/- mice ( n =8) and porcine pancreatic elastase (PPE) instillation in C57BL/6 wildtype mice ( n =12). The lncRNA H19 was identified as one of the most highly up-regulated transcripts in both mouse aneurysm models compared to sham-operated controls...
April 18, 2018: Circulation
https://www.readbyqxmd.com/read/29669758/silencing-of-long-non-coding-rna-mir22hg-triggers-cell-survival-death-signaling-via-oncogenes-ybx1-met-and-p21-in-lung-cancer
#15
Wenmei Su, Shumei Feng, Xiuyuan Chen, Xia Yang, Rui Mao, Chunfang Guo, Zhuwen Wang, Dafydd G Thomas, Jules Lin, Rishindra M Reddy, Mark B Orringer, Andrew C Chang, Zhixiong Yang, David G Beer, Guoan Chen
The long non-coding RNA (lncRNA) MIR22HG has previously been identified as a prognostic marker in hepatocellular carcinoma. Here we performed a comprehensive analysis of lncRNA expression profiles from RNA-seq data and report that MIR22HG plays a similar role in lung cancer. Analysis of 918 lung cancer and normal lung tissues and lung cancer cell lines revealed that MIR22HG was significantly downregulated in lung cancer; this decreased expression was associated with poor patient survival. MIR22HG bound and stabilized the YBX1 protein...
April 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29669301/lin28b-promotes-the-progression-of-colon-cancer-by-increasing-b-cell-lymphoma-2-expression
#16
Leilei Yuan, Junhong Tian
RNA-binding protein LIN28B is frequently overexpressed in human colon cancer and is associated with the tumor progression and poor prognosis. The potential molecular mechanisms underlying the role of LIN28B in colon cancer remain unclear. The present study aimed to explore the role of B-cell lymphoma 2 (BCL-2) in promoting colon cancer development associated with LIN28B. The expression pattern of LIN28B in colon cancer tissues and cell lines was detected by RT-PCR, Western blotting analysis, and immunohistochemical staining...
April 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29669287/zranb1-is-an-ezh2-deubiquitinase-and-a-potential-therapeutic-target-in-breast-cancer
#17
Peijing Zhang, Zhenna Xiao, Shouyu Wang, Mutian Zhang, Yongkun Wei, Qinglei Hang, Jongchan Kim, Fan Yao, Cristian Rodriguez-Aguayo, Baochau N Ton, Minjung Lee, Yumeng Wang, Zhicheng Zhou, Liyong Zeng, Xiaoyu Hu, Sarah E Lawhon, Ashley N Siverly, Xiaohua Su, Jia Li, Xiaoping Xie, Xuhong Cheng, Liang-Chiu Liu, Hui-Wen Chang, Shu-Fen Chiang, Gabriel Lopez-Berestein, Anil K Sood, Junjie Chen, M James You, Shao-Cong Sun, Han Liang, Yun Huang, Xianbin Yang, Deqiang Sun, Yutong Sun, Mien-Chie Hung, Li Ma
Although EZH2 enzymatic inhibitors have shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond because EZH2 can promote cancer independently of its histone methyltransferase activity. Here we identify ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2. Depletion of ZRANB1 in breast cancer cells results in EZH2 destabilization and growth inhibition. Systemic delivery of ZRANB1 small interfering RNA (siRNA) leads to marked antitumor and antimetastatic effects in preclinical models of triple-negative breast cancer (TNBC)...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669280/the-long-non-coding-rna-lnc-31-interacts-with-rock1-mrna-and-mediates-its-yb-1-dependent-translation
#18
Dacia Dimartino, Alessio Colantoni, Monica Ballarino, Julie Martone, Davide Mariani, Johannes Danner, Astrid Bruckmann, Gunter Meister, Mariangela Morlando, Irene Bozzoni
Cytoplasmic long non-coding RNAs have been shown to act at many different levels to control post-transcriptional gene expression, although their role in translational control is poorly understood. Here, we show that lnc-31, a non-coding RNA required for myoblast proliferation, promotes ROCK1 protein synthesis by stabilizing its translational activator, YB-1. We find that lnc-31 binds to the Rock1 mRNA as well as to the YB-1 protein and that translational activation requires physical interaction between the two RNA species...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29667684/interaction-of-na-k-mg-2-and-ca-2-counter-cations-with-rna
#19
REVIEW
Stefan K Kolev, Petko St Petkov, Miroslav A Rangelov, Dimitar V Trifonov, Teodor I Milenov, Georgi N Vayssilov
Alkaline and alkaline earth ions, namely Na+, K+, Mg2+ and Ca2+, are critical for the stability, proper folding and functioning of RNA. Moreover, those metal ions help to facilitate macromolecular interactions as well as the formation of supramolecular structures (e.g. the ribosome and the ribozymes). Therefore, identifying the interactions between ions and nucleic acids is a key to the better comprehension of the physical nature and biological functions of those biomolecules. The scope of this review is to highlight the preferential location and binding sites of alkaline and alkaline earth metal ions compensating the negatively charged backbone of nucleic acids and interacting with other electronegative centers, focusing on RNA...
April 18, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29667478/retro-inverso-follicle-stimulating-hormone-peptide-mediated-polyethylenimine-complexes-for-targeted-ovarian-cancer-gene-therapy
#20
Mengyu Zhang, Mingxing Zhang, Jing Wang, Qingqing Cai, Ran Zhao, Yi Yu, Haiyan Tai, Xiaoyan Zhang, Congjian Xu
BACKGROUND: The development of nanoparticle drug delivery systems with targeted ligands has the potential to increase treatment efficiency in ovarian cancer. METHODS: We developed a 21-amino acid peptide, YTRDLVYGDPARPGIQGTGTF (L-FP21) conjugated to polyethylenimine (PEI) and methoxy polyethylene glycol (mPEG) to prepare a nanoparticle drug vehicle to target follicle-stimulating hormone receptor (FSHR) in ovarian cancer. At the same time, we optimized the ligand of the nanoparticle vehicle using D-peptides, which consist of D-amino acids (D-FP21)...
November 2018: Drug Delivery
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