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Dania Al Labban, Seung-Hee Jo, Paola Ostano, Chiara Saglietti, Massimo Bongiovanni, Renato Panizzon, G Paolo Dotto
Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung...
May 14, 2018: Journal of Clinical Investigation
Gabrielle Perron, Pouria Jandaghi, Shraddha Solanki, Maryam Safisamghabadi, Cristina Storoz, Mehran Karimzadeh, Andreas I Papadakis, Madeleine Arseneault, Ghislaine Scelo, Rosamonde E Banks, Jorg Tost, Mark Lathrop, Simon Tanguay, Alvis Brazma, Sidong Huang, Fadi Brimo, Hamed S Najafabadi, Yasser Riazalhosseini
Widespread remodeling of the transcriptome is a signature of cancer; however, little is known about the post-transcriptional regulatory factors, including RNA-binding proteins (RBPs) that regulate mRNA stability, and the extent to which RBPs contribute to cancer-associated pathways. Here, by modeling the global change in gene expression based on the effect of sequence-specific RBPs on mRNA stability, we show that RBP-mediated stability programs are recurrently deregulated in cancerous tissues. Particularly, we uncovered several RBPs that contribute to the abnormal transcriptome of renal cell carcinoma (RCC), including PCBP2, ESRP2, and MBNL2...
May 8, 2018: Cell Reports
Bin Wang, Guang Wang, Fei Shen, Shijiang Zhu
Plant glycine-rich RNA-binding proteins (GR-RBPs) have been shown to play important roles in response to abiotic stresses in actively proliferating organs such as young plants, root tips, and flowers, but their roles in chilling responses of harvested fruit remains largely unknown. Here, we investigated the role of CsGR-RBP3 in the chilling response of cucumber fruit. Pre-storage cold acclimation at 10°C (PsCA) for 3 days significantly enhanced chilling tolerance of cucumber fruit compared with the control fruit that were stored at 5°C...
2018: Frontiers in Plant Science
Zhiting Zhang, Qianqian Guo, Shufang Zhang, Chenxi Xiang, Xinwei Guo, Feng Zhang, Lanlan Gao, Haiwei Ni, Tao Xi, Lufeng Zheng
RNA binding proteins (RBPs) are pivotal post-transcriptional regulators. RNPC1, an RBP, acts as a tumor suppressor through binding and regulating the expression of target genes in cancer cells. This study disclosed that RNPC1 expression was positively correlated with breast cancer patients' relapse free and overall survival, and RNPC1suppressed breast cancer cells metastasis. Mechanistically, RNPC1 promoting a competing endogenous network (ceRNA) crosstalk between STARD13, CDH5, HOXD10, and HOXD1 (STARD13-correlated ceRNA network) that we previously confirmed in breast cancer cells through stabilizing the transcripts and thus facilitating the expression of these four genes in breast cancer cells...
May 7, 2018: Molecular Pharmaceutics
Pierre Baldi, Peter Sadowski, Zhiqin Lu
Random backpropagation (RBP) is a variant of the backpropagation algorithm for training neural networks, where the transpose of the forward matrices are replaced by fixed random matrices in the calculation of the weight updates. It is remarkable both because of its effectiveness, in spite of using random matrices to communicate error information, and because it completely removes the taxing requirement of maintaining symmetric weights in a physical neural system. To better understand random backpropagation, we first connect it to the notions of local learning and learning channels...
July 2018: Artificial Intelligence
Jennifer R DeRosa, Brandon S Moyer, Ellie Lumen, Aaron J Wolfe, Meegan B Sleeper, Anthony H Bianchi, Ashleigh Crawford, Connor McGuigan, Danique Wortel, Cheyanne Fisher, Kelsey J Moody, Adam R Blanden
Antibodies are the most prolific biologics in research and clinical environments because of their ability to bind targets with high affinity and specificity. However, antibodies also carry liabilities. A significant portion of the life science reproducibility crisis is driven by inconsistent performance of research-grade antibodies, and clinical antibodies are often unstable and require costly cold chain management to reach their destinations in active form. In biotechnology, antibodies are also limited by difficulty integrating them in many recombinant systems due to their size and structural complexity...
May 3, 2018: Biochemistry
Xiaoyong Pan, Hong-Bin Shen
Motivation: RNA-binding proteins (RBPs) take over 5∼10% of the eukaryotic proteome and play key roles in many biological processes, e.g. gene regulation. Experimental detection of RBP binding sites is still time-intensive and high-costly. Instead, computational prediction of the RBP binding sites using pattern learned from existing annotation knowledge is a fast approach. From the biological point of view, the local structure context derived from local sequences will be recognized by specific RBPs...
May 2, 2018: Bioinformatics
Paul D Bieniasz, Sebla B Kutluay
Virtually every step of HIV-1 replication and numerous cellular antiviral defense mechanisms are regulated by the binding of a viral or cellular RNA-binding protein (RBP) to distinct sequence or structural elements on HIV-1 RNAs. Until recently, these protein-RNA interactions were studied largely by in vitro binding assays complemented with genetics approaches. However, these methods are highly limited in the identification of the relevant targets of RBPs in physiologically relevant settings. Development of crosslinking-immunoprecipitation sequencing (CLIP) methodology has revolutionized the analysis of protein-nucleic acid complexes...
May 2, 2018: Retrovirology
Jiaqi Gu, Ming Wang, Yang Yang, Ding Qiu, Yiqun Zhang, Jinbiao Ma, Yu Zhou, Gregory J Hannon, Yang Yu
Protein-RNA interaction networks are essential to understand gene regulation control. Identifying binding sites of RNA-binding proteins (RBPs) by the UV-crosslinking and immunoprecipitation (CLIP) represents one of the most powerful methods to map protein-RNA interactions in vivo. However, the traditional CLIP protocol is technically challenging, which requires radioactive labeling and suffers from material loss during PAGE-membrane transfer procedures. Here we introduce a super-efficient CLIP method (GoldCLIP) that omits all gel purification steps...
April 27, 2018: Genomics, Proteomics & Bioinformatics
Luisa Statello, Marco Maugeri, Elena Garre, Muhammad Nawaz, Jessica Wahlgren, Alexandros Papadimitriou, Christina Lundqvist, Lennart Lindfors, Anna Collén, Per Sunnerhagen, Marco Ragusa, Michele Purrello, Cinzia Di Pietro, Natalie Tigue, Hadi Valadi
The RNA that is packaged into exosomes is termed as exosomal-shuttle RNA (esRNA); however, the players, which take this subset of RNA (esRNA) into exosomes, remain largely unknown. We hypothesized that RNA binding proteins (RBPs) could serve as key players in this mechanism, by making complexes with RNAs and transporting them into exosomes during the biosynthesis of exosomes. Here, we demonstrate the presence of 30 RBPs in exosomes that were shown to form RNA-RBP complexes with both cellular RNA and exosomal-RNA species...
2018: PloS One
Lin Guo, Hong Joo Kim, Hejia Wang, John Monaghan, Fernande Freyermuth, Julie C Sung, Kevin O'Donovan, Charlotte M Fare, Zamia Diaz, Nikita Singh, Zi Chao Zhang, Maura Coughlin, Elizabeth A Sweeny, Morgan E DeSantis, Meredith E Jackrel, Christopher B Rodell, Jason A Burdick, Oliver D King, Aaron D Gitler, Clotilde Lagier-Tourenne, Udai Bhan Pandey, Yuh Min Chook, J Paul Taylor, James Shorter
RNA-binding proteins (RBPs) with prion-like domains (PrLDs) phase transition to functional liquids, which can mature into aberrant hydrogels composed of pathological fibrils that underpin fatal neurodegenerative disorders. Several nuclear RBPs with PrLDs, including TDP-43, FUS, hnRNPA1, and hnRNPA2, mislocalize to cytoplasmic inclusions in neurodegenerative disorders, and mutations in their PrLDs can accelerate fibrillization and cause disease. Here, we establish that nuclear-import receptors (NIRs) specifically chaperone and potently disaggregate wild-type and disease-linked RBPs bearing a NLS...
April 19, 2018: Cell
Boon C Ng, Matthias Kleinheyer, Peter A Smith, Daniel Timms, William E Cohn, Einly Lim
Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction...
2018: PloS One
Saakshi Jalali, Shrey Gandhi, Vinod Scaria
Background: Long non-coding RNAs (lncRNAs), are being reported to be extensively involved in diverse regulatory roles and have exhibited numerous disease associations. LncRNAs modulate their function through interaction with other biomolecules in the cell including DNA, RNA, and proteins. The availability of genome-scale experimental datasets of RNA binding proteins (RBP) motivated us to understand the role of lncRNAs in terms of its interactions with these proteins. In the current report, we demonstrate a comprehensive study of interactions between RBP and lncRNAs at a transcriptome scale through extensive analysis of the crosslinking and immunoprecipitation (CLIP) experimental datasets available for 70 RNA binding proteins...
2018: Frontiers in Molecular Biosciences
Wei Tang, Xian Li, Zhen-Zhuo Ma, Chun-Ying Li
OBJECTIVE: To investigate the expression of retinol-binding protein (RBP) in patients with acute myeloid leukemia (AML) and its related factors. METHODS: The clinical data of 123 patients with AML from October 2012 to February 2016 and 100 healthy controls were collected and the correlation of RBP expression level with sex, French-American-British (FAB) subtypes, molecular mutations, peripheral white blood cells and long-term outcomes was analyzed. RESULTS: Compared with AML patients, the RBP expression level was significantly higher in healthy controls (61...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Hiroshi I Suzuki, Ryan M Spengler, Giedre Grigelioniene, Tatsuya Kobayashi, Phillip A Sharp
RNA interference (RNAi) is a major, powerful platform for gene perturbations, but is restricted by off-target mechanisms. Communication between RNAs, small RNAs, and RNA-binding proteins (RBPs) is a pervasive feature of cellular RNA networks. We present a crosstalk scenario, designated as crosstalk with endogenous RBPs' (ceRBP), in which small interfering RNAs or microRNAs with seed sequences that overlap RBP motifs have extended biological effects by perturbing endogenous RBP activity. Systematic analysis of small interfering RNA (siRNA) off-target data and genome-wide RNAi cancer lethality screens using 501 human cancer cell lines, a cancer dependency map, identified that seed-to-RBP crosstalk is widespread, contributes to off-target activity, and affects RNAi performance...
May 2018: Nature Genetics
Qingyan Zhang, Chunming Jiang, Tianfeng Tang, Hengjin Wang, Yangyang Xia, Qiuyuan Shao, Miao Zhang
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is often accompanied with tubulointerstitial lesion. This study aimed to assess the role of urinary biomarkers in predicting tubulointerstitial lesion and treatment response in FSGS patients. METHODS: Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG) and retinol-binding protein (RBP) were measured in 32 FSGS patients and 22 patients with minimal change nephrotic syndrome...
April 2018: American Journal of the Medical Sciences
Eunji Choi, Jungju Oh, Dahee Lee, Jaewon Lee, Xiaonan Tan, Minkyung Kim, Gyeungyun Kim, Chunxian Piao, Minhyung Lee
The receptor for advanced glycation end-products (RAGE) is involved in tumor angiogenesis. Inhibition of RAGE might be an effective anti-angiogenic therapy for cancer. In this study, a cationic RAGE-binding peptide (RBP) was produced as an antagonist of RAGE, and a ternary-complex consisting of RBP, polyethylenimine (2 kDa, PEI2k), and a suicide gene (pHSVtk) was developed as a gene delivery system with dual functions: the anti-tumor effect of pHSVtk and anti-angiogenic effect of RBP. As an antagonist of RAGE, RBP decreased the secretion of vascular-endothelial growth factor (VEGF) in activated macrophages and reduced the tube-formation of endothelial cells in vitro...
April 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xingxia Liu, Shaoda Ren, Chaozhuo Ge, Kai Cheng, Xiaojing Li, Robert Chunhua Zhao
Mesenchymal stem cells (MSCs) have a superior immunomodulatory capacity compared to other cells of the immune system, and they hold great promise for treating various immune disorders. However, their regulatory effects on the maturation of immature dendritic cells (imDCs) are not fully understood. In this study, we show that Sca-1+ Lin- CD117- MSCs restrain the lipopolysaccharide-stimulated maturation transition of imDCs cocultured without exogenous cytokines. The Notch signaling pathway plays a critical role in the process by controlling interferon regulatory factor 8 (IRF8) expression in an RBP-J-dependent manner...
April 15, 2018: Stem Cells and Development
Yali Jiang, Yuanyuan Wang, Pengfei Ma, Dongjie An, Junlong Zhao, Shiqian Liang, Yuchen Ye, Yingying Lu, Peng Zhang, Xiaowei Liu, Hua Han, Hongyan Qin
Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β...
April 11, 2018: Protein & Cell
F X Reymond Sutandy, Stefanie Ebersberger, Lu Huang, Anke Busch, Maximilian Bach, Hyun-Seo Kang, Jörg Fallmann, Daniel Maticzka, Rolf Backofen, Peter F Stadler, Kathi Zarnack, Michael Sattler, Stefan Legewie, Julian König
Alternative splicing generates distinct mRNA isoforms and is crucial for proteome diversity in eukaryotes. The RNA-binding protein (RBP) U2AF2 is central to splicing decisions, as it recognizes 3' splice sites and recruits the spliceosome. We establish "in vitro iCLIP" experiments, in which recombinant RBPs are incubated with long transcripts, to study how U2AF2 recognizes RNA sequences and how this is modulated by trans -acting RBPs. We measure U2AF2 affinities at hundreds of binding sites and compare in vitro and in vivo binding landscapes by mathematical modeling...
April 11, 2018: Genome Research
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