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I C Haznedaroglu, U Y Malkan
The existence of a local renin-angiotensin system (RAS) specific to the hematopoietic bone marrow (BM) microenvironment had been proposed two decades ago. Most of the RAS molecules including ACE, ACE2, AGT, AGTR1, AGTR2, AKR1C4, AKR1D1, ANPEP, ATP6AP2, CMA1, CPA3, CTSA, CTSD, CTSG, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DPP3, EGFR, ENPEP, GPER, HSD11B1, HSD11B2, IGF2R, KLK1, LNPEP, MAS1, MME, NR3C1, NR3C2, PREP, REN, RNPEP, and THOP1 are locally present in the BM microenvironment. Local BM RAS peptides control the hematopoietic niche, myelopoiesis, erythropoiesis, thrombopoiesis and the development of other cellular lineages...
October 2016: European Review for Medical and Pharmacological Sciences
Makoto Hirano, Kiichiro Totani, Tomohiko Fukuda, Jianguo Gu, Akemi Suzuki
BACKGROUND: Megalin is a 600-kDa single-spanning transmembrane glycoprotein and functions as an endocytic receptor, distributed not only in the kidney but also in other tissues. Structurally and functionally distinct ligands for megalin have been identified. Megalin has 30 potential N-glycosylation sites in its extracellular domain. We found that megalin interacts with its ligands in a glycoform-dependent manner. METHODS: Distribution of megalin and glycans was histochemically analyzed in mouse kidneys...
October 20, 2016: Biochimica et Biophysica Acta
Lili Gu, Hyun Ju Jung, Kyung Jin Kwak, Sy Nguyen Dinh, Yeon-Ok Kim, Hunseung Kang
Despite an increasing understanding of the essential role of the Mei2 gene encoding an RNA-binding protein (RBP) in premeiotic DNA synthesis and meiosis in yeasts and animals, the functional roles of the mei2-like genes in plant growth and development are largely unknown. Contrary to other mei2-like RBPs that contain three RNA-recognition motifs (RRMs), the mei2 C-terminal RRM only (MCT) is unique in that it harbors only the last C-terminal RRM. Although MCTs have been implicated to play important roles in plants, their functional roles in stress responses as well as plant growth and development are still unknown...
October 13, 2016: Plant Physiology and Biochemistry: PPB
Zheng Luo, Qin Yang, Li Yang
RNA sequence motifs are not sufficient for association with RBPs. In this issue of Molecular Cell, Taliaferro et al. (2016) demonstrate that, other than sequence motif, RNA secondary structure plays a repressive role on RBP binding, both in vitro and in vivo.
October 20, 2016: Molecular Cell
Aitor Garzia, Cindy Meyer, Pavel Morozov, Marcin Sajek, Thomas Tuschl
Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) in combination with next-generation sequencing is a powerful method for identifying endogenous targets of RNA-binding proteins (RBPs). Depending on the characteristics of each RBP, key steps in the PAR-CLIP procedure must be optimized. Here we present a comprehensive step-by-step PAR-CLIP protocol with detailed explanations of the critical steps. Furthermore, we report the application of a new PAR-CLIP data analysis pipeline to three distinct RBPs targeting different annotation categories of cellular RNAs...
October 17, 2016: Methods: a Companion to Methods in Enzymology
Jie Dong, Hongbo Dong, Peiyu Ye, Yinkun Yan, Bo Xi, Jie Mi
OBJECTIVE: To validate the accuracy of Raycome RBP-1200 used for blood pressure (BP) measurements in Chinese children aged 3-12 years according to the Association for the Advancement of Medical Instrumentation (AAMI)/International Organization for Standardization 81060-2:2013(E) protocol. METHODS: A prospective observational study was carried out using 'the same arm sequential method' as described in the AAMI protocol. Eighty-seven children participated in this examination and 255 paired-determinations were analyzed...
October 4, 2016: Blood Pressure Monitoring
Cindo O Nicholson, Matthew B Friedersdorf, Jack D Keene
RNA-binding proteins (RBPs) and non-coding RNAs orchestrate post-transcriptional processes through the recognition of specific sites on targeted transcripts. Thus, understanding the connection between binding to specific sites and active regulation of the whole transcript is essential. Many immunoprecipitation techniques have been developed that identify either whole transcripts or binding sites of RBPs on each transcript using cell lysates. However, none of these methods simultaneously measures the strength of each binding site, and quantifies binding to whole transcripts...
October 14, 2016: RNA
Huilian Wang, Xi Lu, Xudong Yang, Nan Xu
BACKGROUND: To date, a definite conclusion about efficiency and safety of tenofovir alafenamide for patients with HIV-1 is not available. The aim of the study was to investigate the efficacy and safety of TAF versus TDF in antiretroviral regimens for patients with HIV-1. METHODS: PUBMED, MEDLINE, and EMBASE database were searched in March 2016, with no language restriction, for randomized controlled trials (RCTs). RESULTS: Six RCTs (n = 5888) met entry criteria...
October 2016: Medicine (Baltimore)
Agnieszka Zwolak, Agnieszka Szuster-Ciesielska, Jadwiga Daniluk, Justyna Semeniuk, Martyna Kandefer-Szerszen
:  Background. Chemerin and retinol binding protein-4 (RBP-4) are adipokines which may play a role in the progression of NAFLD. It has been also suggested that cytokeratin-18 (CK-18) could be a marker of hepatocyte caspase-directed death while transgelin-2 production could reflect stage of liver fibrosis. The aim of this study was to evaluate the level of the above adipokines in sera of patients with NAFLD and determine the relation between the level of transgelin-2 and fibrosis-4 index (FIB-4)...
November 2016: Annals of Hepatology
Marlene Reichel, Yalin Liao, Mandy Rettel, Chikako Ragan, Maurits Evers, Anne-Marie Alleaume, Rastislav Horos, Matthias W Hentze, Thomas Preiss, Anthony A Millar
RNA-binding proteins (RBPs) control the fate and expression of a transcriptome. Despite this fundamental importance, our understanding of plant RBPs is rudimentary, being mainly derived via bioinformatic extrapolation from other kingdoms. Here, we have adapted the mRNA-protein interactome capture method to investigate the RNA-binding proteome in planta. From Arabidopsis thaliana (At) etiolated seedlings, we captured more than 700 proteins, including 300 with high confidence that we have defined as the At-RBP set...
October 11, 2016: Plant Cell
Tzu-Fang Lou, Chase A Weidmann, Jordan Killingsworth, Traci M Tanaka Hall, Aaron C Goldstrohm, Zachary T Campbell
RNA-binding proteins (RBPs) collaborate to control virtually every aspect of RNA function. Tremendous progress has been made in the area of global assessment of RBP specificity using next-generation sequencing approaches both in vivo and in vitro. Understanding how protein-protein interactions enable precise combinatorial regulation of RNA remains a significant problem. Addressing this challenge requires tools that can quantitatively determine the specificities of both individual proteins and multimeric complexes in an unbiased and comprehensive way...
October 8, 2016: Methods: a Companion to Methods in Enzymology
Shu-Hong Wang, Qing-Yang Lu, Ya-Huan Guo, Yuan-Yuan Song, Pei-Jun Liu, Yao-Chun Wang
Myeloid-derived suppressor cells (MDSCs) mostly consisting of polymorphonuclear (PMN)-MDSCs and mononuclear MDSCs have been considered to play critical roles in immunosuppression, angiogenesis, invasion and metastases of various tumours. However, it is still unclear the regulated mechanisms underlying the generation and immunosuppression of two major MDSC subsets. Here, we report Notch signalling was inhibited significantly in tumour-bearing mouse MDSCs, in which PMN-MDSCs were the major population. MDSCs without recombination signal binding protein-Jк (RBP-J), the critical transcription factor mediating signalling from all four mammalian Notch receptors, reduced their ability of inhibiting the proliferation and activation of allogenic T cells...
October 8, 2016: European Journal of Cancer
K Steinhäuser, P Klöble, N-N Kreis, A Ritter, A Friemel, S Roth, J M Reichel, J Michaelis, M A Rieger, F Louwen, F Oswald, J Yuan
Deregulation of mitotic microtubule (MT) dynamics results in defective spindle assembly and chromosome missegregation, leading further to chromosome instability, a hallmark of tumor cells. RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signaling pathway. Intriguingly, deregulated RITA is involved in primary hepatocellular carcinoma and other malignant entities. We were interested in the potential molecular mechanisms behind its involvement. We show here that RITA binds to tubulin and localizes to various mitotic MT structures...
October 10, 2016: Oncogene
Kristopher W Brannan, Wenhao Jin, Stephanie C Huelga, Charles A S Banks, Joshua M Gilmore, Laurence Florens, Michael P Washburn, Eric L Van Nostrand, Gabriel A Pratt, Marie K Schwinn, Danette L Daniels, Gene W Yeo
RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs. This motivated SONAR, a computational approach that predicts RNA binding activity by analyzing large-scale affinity precipitation-MS protein-protein interactomes...
October 20, 2016: Molecular Cell
J Matthew Taliaferro, Nicole J Lambert, Peter H Sudmant, Daniel Dominguez, Jason J Merkin, Maria S Alexis, Cassandra A Bazile, Christopher B Burge
Many RNA binding proteins (RBPs) bind specific RNA sequence motifs, but only a small fraction (∼15%-40%) of RBP motif occurrences are occupied in vivo. To determine which contextual features discriminate between bound and unbound motifs, we performed an in vitro binding assay using 12,000 mouse RNA sequences with the RBPs MBNL1 and RBFOX2. Surprisingly, the strength of binding to motif occurrences in vitro was significantly correlated with in vivo binding, developmental regulation, and evolutionary age of alternative splicing...
October 20, 2016: Molecular Cell
Pritha Ghosh, Oommen K Mathew, Ramanathan Sowdhamini
BACKGROUND: RNA-binding proteins (RBPs) interact with their cognate RNA(s) to form large biomolecular assemblies. They are versatile in their functionality and are involved in a myriad of processes inside the cell. RBPs with similar structural features and common biological functions are grouped together into families and superfamilies. It will be useful to obtain an early understanding and association of RNA-binding property of sequences of gene products. Here, we report a web server, RStrucFam, to predict the structure, type of cognate RNA(s) and function(s) of proteins, where possible, from mere sequence information...
October 7, 2016: BMC Bioinformatics
Rikard G Fred, Syrina Mehrabi, Christopher M Adams, Nils Welsh
OBJECTIVES: Insulin expression is highly controlled on the posttranscriptional level. The RNA binding proteins (RBPs) responsible for this result are still largely unknown. METHODS AND RESULTS: To identify RBPs that bind to insulin mRNA we performed mass spectrometry analysis on proteins that bound synthetic oligonucloetides mimicing the 5'- and the 3'-untranslated regions (UTRs) of rat and human insulin mRNA in vitro. We observed that the RBPs heterogeneous nuclear ribonucleoprotein (hnRNP) U, polypyrimidine tract binding protein (PTB), hnRNP L and T-cell restricted intracellular antigen 1-related protein (TIA-1-related protein; TIAR) bind to insulin mRNA sequences, and that the in vitro binding affinity of these RBPs changed when INS-1 cells were exposed to glucose, 3-isobutyl-1-methylxanthine (IBMX) or nitric oxide...
September 2016: Heliyon
Aditi Khandekar, Steven Springer, Wei Wang, Stephanie Hicks, Carla J Weinheimer, Ramon Diaz-Trelles, Jeanne M Nerbonne, Stacey Rentschler
RATIONALE: Ventricular arrhythmias often arise from the Purkinje-myocyte junction and are a leading cause of sudden cardiac death. Notch activation reprograms cardiac myocytes to an "induced Purkinje-like" state characterized by prolonged action potential duration and expression of Purkinje enriched genes. OBJECTIVE: To understand the mechanism by which canonical Notch signaling causes action potential prolongation. METHODS AND RESULTS: We find that endogenous Purkinje cells have reduced peak K(+) current, Ito and IK,slow when compared with ventricular myocytes...
October 3, 2016: Circulation Research
Heng-Chao Yu, Lu Bai, Zhao-Xu Yang, Hong-Yan Qin, Kai-Shan Tao, Hua Han, Ke-Feng Dou
Ischemia-reperfusion (I/R) is a major reason of hepatocyte injury during liver surgery and transplantation. Myeloid cells including macrophages and neutrophils play important roles in sustained tissue inflammation and damage, but the mechanisms regulating myeloid cells activity have been elusive. In this study, we investigate the role of Notch signaling in myeloid cells during hepatic I/R injury by using a mouse model of myeloid specific conditional knockout of RBP-J. Myeloid-specific RBP-J deletion alleviated hepatic I/R injury...
September 29, 2016: Scientific Reports
Mehrpouya B Mobin, Stefanie Gerstberger, Daniel Teupser, Benedetta Campana, Klaus Charisse, Markus H Heim, Muthiah Manoharan, Thomas Tuschl, Markus Stoffel
The liver is essential for the synthesis of plasma proteins and integration of lipid metabolism. While the role of transcriptional networks in these processes is increasingly understood, less is known about post-transcriptional control of gene expression by RNA-binding proteins (RBPs). Here, we show that the RBP vigilin is upregulated in livers of obese mice and in patients with fatty liver disease. By using in vivo, biochemical and genomic approaches, we demonstrate that vigilin controls very-low-density lipoprotein (VLDL) secretion through the modulation of apolipoproteinB/Apob mRNA translation...
2016: Nature Communications
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