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Waleed S Albihlal, André P Gerber
RNA-binding proteins play essential roles in the post-transcriptional regulation of gene expression. While hundreds of RNA-binding proteins can be predicted computationally, the recent introduction of proteome-wide approaches has dramatically expanded the repertoire of proteins interacting with RNA. Besides canonical RNA-binding proteins that contain characteristic RNA-binding domains, many proteins that lack such domains but have other well-characterised cellular functions were identified; including metabolic enzymes, heat shock proteins, kinases, as well as transcription factors and chromatin-associated proteins...
June 16, 2018: FEBS Letters
Anaïs Portet, Richard Galinier, Silvain Pinaud, Julien Portela, Fanny Nowacki, Benjamin Gourbal, David Duval
Insect thioester-containing protein (iTEP) is the most recently defined group among the thioester-containing protein (TEP) superfamily. TEPs are key components of the immune system, and iTEPs from flies and mosquitoes were shown to be major immune weapons. Initially characterized from insects, TEP genes homologous to iTEP were further described from several other invertebrates including arthropods, cniderians, and mollusks albeit with few functional characterizations. In the freshwater snail Biomphalaria glabrata , a vector of the schistosomiasis disease, the presence of a TEP protein (BgTEP) was previously described in a well-defined immune complex involving snail lectins (fibrinogen-related proteins) and schistosome parasite mucins (SmPoMuc)...
2018: Frontiers in Immunology
Hadia Ahmed, T C Howton, Yali Sun, Natascha Weinberger, Youssef Belkhadir, M Shahid Mukhtar
In all organisms, major biological processes are controlled by complex protein-protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1MAIN ). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1MAIN and are preferential targets of pathogen effectors...
June 13, 2018: Nature Communications
Evangelia K Papachristou, Kamal Kishore, Andrew N Holding, Kate Harvey, Theodoros I Roumeliotis, Chandra Sekhar Reddy Chilamakuri, Soleilmane Omarjee, Kee Ming Chia, Alex Swarbrick, Elgene Lim, Florian Markowetz, Matthew Eldridge, Rasmus Siersbaek, Clive S D'Santos, Jason S Carroll
Understanding the dynamics of endogenous protein-protein interactions in complex networks is pivotal in deciphering disease mechanisms. To enable the in-depth analysis of protein interactions in chromatin-associated protein complexes, we have previously developed a method termed RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins). Here, we present a quantitative multiplexed method (qPLEX-RIME), which integrates RIME with isobaric labelling and tribrid mass spectrometry for the study of protein interactome dynamics in a quantitative fashion with increased sensitivity...
June 13, 2018: Nature Communications
Raffaele Ferrari, Demis A Kia, James E Tomkins, John Hardy, Nicholas W Wood, Ruth C Lovering, Patrick A Lewis, Claudia Manzoni
BACKGROUND: Genome wide association studies (GWAS) have helped identify large numbers of genetic loci that significantly associate with increased risk of developing diseases. However, translating genetic knowledge into understanding of the molecular mechanisms underpinning disease (i.e. disease-specific impacted biological processes) has to date proved to be a major challenge. This is primarily due to difficulties in confidently defining candidate genes at GWAS-risk loci. The goal of this study was to better characterize candidate genes within GWAS loci using a protein interactome based approach and with Parkinson's disease (PD) data as a test case...
June 13, 2018: BMC Genomics
Ingoo Lee, Hojung Nam
BACKGROUND: Identification of drug-target interactions acts as a key role in drug discovery. However, identifying drug-target interactions via in-vitro, in-vivo experiments are very laborious, time-consuming. Thus, predicting drug-target interactions by using computational approaches is a good alternative. In recent studies, many feature-based and similarity-based machine learning approaches have shown promising results in drug-target interaction predictions. A previous study showed that accounting connectivity information of drug-drug and protein-protein interactions increase performances of prediction by the concept of 'guilt-by-association'...
June 13, 2018: BMC Bioinformatics
Siwei Chen, Robert Fragoza, Lambertus Klei, Yuan Liu, Jiebiao Wang, Kathryn Roeder, Bernie Devlin, Haiyuan Yu
Identifying disease-associated missense mutations remains a challenge, especially in large-scale sequencing studies. Here we establish an experimentally and computationally integrated approach to investigate the functional impact of missense mutations in the context of the human interactome network and test our approach by analyzing ~2,000 de novo missense mutations found in autism subjects and their unaffected siblings. Interaction-disrupting de novo missense mutations are more common in autism probands, principally affect hub proteins, and disrupt a significantly higher fraction of hub interactions than in unaffected siblings...
June 11, 2018: Nature Genetics
Victor Faundez, Ilario De Toma, Barbara Bardoni, Renata Bartesaghi, Dean Nizetic, Rafael de la Torre, Roi Cohen Kadosh, Yann Herault, Mara Dierssen, Marie-Claude Potier
Ongoing treatments for genetic developmental disorders of the central nervous system are mostly symptomatic and do not correct the genetic cause. Recent identification of common mechanisms between diseases has suggested that new therapeutic targets could be applied across intellectual disabilities with potential disease-modifying properties. The European Down syndrome and other genetic developmental disorders (DSG2D) network joined basic and clinical scientists to foster this research and carry out clinical trials...
June 7, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Binkai Chi, Jeremy D O'Connell, Tomohiro Yamazaki, Jaya Gangopadhyay, Steven P Gygi, Robin Reed
Mutations in multiple RNA/DNA binding proteins cause Amyotrophic Lateral Sclerosis (ALS). Included among these are the three members of the FET family (FUS, EWSR1 and TAF15) and the structurally similar MATR3. Here, we characterized the interactomes of these four proteins, revealing that they largely have unique interactors, but share in common an association with U1 snRNP. The latter observation led us to analyze the interactome of the U1 snRNP machinery. Surprisingly, this analysis revealed the interactome contains ~220 components, and of these, >200 are shared with the RNA polymerase II (RNAP II) machinery...
June 8, 2018: Scientific Reports
Silvia Sookoian, Diego Flichman, Martin E Garaycoechea, Julio San Martino, Gustavo O Castaño, Carlos J Pirola
Long noncoding RNAs (lncRNAs) are functional molecules that orchestrate gene expression. To identify lncRNAs involved in nonalcoholic fatty liver disease (NAFLD) severity, we performed a multiscale study that included: (a) systems biology modeling that indicated metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) as a candidate lncRNA for exploring disease-related associations, (b) translational exploration in the clinical setting, and (c) mechanistic modeling. MALAT1 liver profiling was performed in three consecutive phases, including an exploratory stage (liver samples from patients with NAFLD who were morbidly obese [n = 47] and from 13 individuals with normal liver histology); a replication stage (patients with NAFLD and metabolic syndrome [n =49]); and a hypothesis-driven stage (patients with chronic hepatitis C and autoimmune liver diseases, [n = 65])...
June 2018: Hepatology Communications
Ayşe Kılıç, Marc Santolini, Taiji Nakano, Matthias Schiller, Mizue Teranishi, Pascal Gellert, Yuliya Ponomareva, Thomas Braun, Shizuka Uchida, Scott T Weiss, Amitabh Sharma, Harald Renz
Allergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including microRNAs (miRs), are pivotal in maintaining immune homeostasis. Since an altered expression of various miRs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRs control mechanisms ensuring Th2 stability and maintenance in the lung...
June 7, 2018: JCI Insight
Alexander C Robeson, Kelly R Lindblom, Jeffrey Wojton, Sally Kornbluth, Kenkyo Matsuura
Caspase-2 has been shown to initiate apoptotic cell death in response to specific intracellular stressors such as DNA damage. However, the molecular mechanisms immediately upstream of its activation are still poorly understood. We combined a caspase-2 bimolecular fluorescence complementation (BiFC) system with fluorophore-specific immunoprecipitation to isolate and study the active caspase-2 dimer and its interactome. Using this technique, we found that tumor necrosis factor receptor-associated factor 2 (TRAF2), as well as TRAF1 and 3, directly binds to the active caspase-2 dimer...
June 6, 2018: EMBO Journal
César Rivera, Flávia Silva Zandonadi, Celeste Sánchez-Romero, Ciro Dantas Soares, Daniela Campos Granato, Wilfredo Alejandro González-Arriagada, Adriana Franco Paes Leme
BACKGROUND: The extracellular matrix modulates the hallmarks of cancer. Here we examined the role of agrin-a member of this matrix-in progression of oral squamous cell carcinoma (OSCC). METHODS: We evaluated the immunohistochemical expression of agrin in OSCC and dysplasias. Benign lesions were used as control. In subsequent experiments, we investigated whether the silencing of agrin interferes with tumour expansion both in vitro as well as in vivo. To gain insights into the role of agrin, we identified its protein network (interactome) using mass spectrometry-based proteomics and bioinformatics...
June 6, 2018: British Journal of Cancer
Farinaz Ghodrati, Mohadeseh Mehrabian, Declan Williams, Ondrej Halgas, Matthew E C Bourkas, Joel C Watts, Emil F Pai, Gerold Schmitt-Ulms
At times, it can be difficult to discern if a lack of overlap in reported interactions for a protein-of-interest reflects differences in methodology or biology. In such instances, systematic analyses of protein-protein networks across diverse paradigms can provide valuable insights. Here, we interrogated the interactome of the prion protein (PrP), best known for its central role in prion diseases, in four mouse cell lines. Analyses made use of identical affinity capture and sample processing workflows. Negative controls were generated from PrP knockout lines of the respective cell models, and the relative levels of peptides were quantified using isobaric labels...
June 5, 2018: Scientific Reports
Michiel Bontinck, Jelle Van Leene, Astrid Gadeyne, Bert De Rybel, Dominique Eeckhout, Hilde Nelissen, Geert De Jaeger
Because virtually all proteins interact with other proteins, studying protein-protein interactions (PPIs) is fundamental in understanding protein function. This is especially true when studying specific developmental processes, in which proteins often make developmental stage- or tissue specific interactions. However, studying these specific PPIs in planta can be challenging. One of the most widely adopted methods to study PPIs in planta is affinity purification coupled to mass spectrometry (AP/MS). Recent developments in the field of mass spectrometry have boosted applications of AP/MS in a developmental context...
2018: Frontiers in Plant Science
Neeti Sanan-Mishra, Anita Tripathi, Kavita Goswami, Rohit N Shukla, Madavan Vasudevan, Hitesh Goswami
ARMOUR was developed as A Rice miRNA:mRNA interaction resource. This informative and interactive database includes the experimentally validated expression profiles of miRNAs under different developmental and abiotic stress conditions across seven Indian rice cultivars. This comprehensive database covers 689 known and 1664 predicted novel miRNAs and their expression profiles in more than 38 different tissues or conditions along with their predicted/known target transcripts. The understanding of miRNA:mRNA interactome in regulation of functional cellular machinery is supported by the sequence information of the mature and hairpin structures...
2018: Frontiers in Plant Science
Hao Nan, Jixun Lan, Mengmeng Tian, Shan Dong, Jiao Tian, Long Liu, Xiaodong Xu, Hongying Chen
The RNA synthesis of porcine reproductive and respiratory syndrome virus (PRRSV), a positive-strand RNA virus, is compartmentalized in virus-induced double-membrane vesicles where viral proteins and some cellular proteins assemble into replication and transcription complexes (RTCs). The viral replicase proteins are the major components of the RTCs but the physical associations among these non-structural proteins (nsps) remain elusive. In this study, we investigated the potential interactions between PRRSV nsps by yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC) and pull-down assays...
2018: Frontiers in Microbiology
Qiao Wang, Qinghe Li, Tao Liu, Guobin Chang, Zhihao Sun, Zhao Gao, Fei Wang, Huaijun Zhou, Ranran Liu, Maiqing Zheng, Huanxian Cui, Guohong Chen, Hua Li, Xiaoya Yuan, Jie Wen, Daxin Peng, Guiping Zhao
PA-N155 and PA-N182 proteins were translated from the 11th and 13th start codon AUG of the RNA polymerase acidic protein (PA) mRNA of H5N1 influenza A virus (IAV), which plays an important role in viral replication. Little is known about the interactions between PA-N155 and PA-N182 and the host proteins. This study investigated the interaction landscape of PA-N155 and PA-N182 of H5N1 IAV in chicken cells while their interacting complexes were captured by immunoprecipitation and analyzed by mass spectrometry...
2018: Frontiers in Microbiology
Yiting Jia, Meili Wang, Chenfeng Mao, Fang Yu, Yingbao Wang, Rui Xiao, Changtao Jiang, Lemin Zheng, Qingbo Xu, Ming Zheng, Yi Fu, Qinghua Hu, Wei Kong
Vascular smooth muscle cells (VSMCs) are highly phenotypically plastic, and loss of the contractile phenotype in VSMCs has been recognized at the early onset of the pathology of a variety of vascular diseases. However, the endogenous regulatory mechanism to maintain contractile phenotype in VSMCs remains elusive. Moreover, little has been known about the role of the mitochondrial bioenergetics in terms of VSMC homeostasis. Herein, we asked if glycoprotein COMP (Cartilage oligomeric matrix protein) is involved in mitochondrial bioenergetics and therefore regulates VSMCs homeostasis...
June 4, 2018: Cell Death & Disease
Sheila V Graham, Jean X Jiang, Marc Mesnil
Since their characterization more than five decades ago, gap junctions and their structural proteins-the connexins-have been associated with cancer cell growth. During that period, the accumulation of data and molecular knowledge about this association revealed an apparent contradictory relationship between them and cancer. It appeared that if gap junctions or connexins can down regulate cancer cell growth they can be also implied in the migration, invasion and metastatic dissemination of cancer cells. Interestingly, in all these situations, connexins seem to be involved through various mechanisms in which they can act either as gap-junctional intercellular communication mediators, modulators of signalling pathways through their interactome, or as hemichannels, which mediate autocrine/paracrine communication...
June 1, 2018: International Journal of Molecular Sciences
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