A5015392819- RNA modifications and cancer
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Retinoids in leukemia and cellular processes
- Neuroblastoma Research and Treatments
- Chemokine receptors and signaling
- Cancer-related molecular mechanisms research
- Cancer, Hypoxia, and Metabolism
- Molecular Biology Techniques and Applications
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Gene expression and cancer classification
- Autophagy in Disease and Therapy
- Osteoarthritis Treatment and Mechanisms
- ATP Synthase and ATPases Research
- Cancer-related gene regulation
- Bioinformatics and Genomic Networks
- Mitochondrial Function and Pathology
- Mesenchymal stem cell research
- Phosphodiesterase function and regulation
- Biochemical Acid Research Studies
- Genetic Mapping and Diversity in Plants and Animals
- Ubiquitin and proteasome pathways
- Advanced Glycation End Products research
- NF-κB Signaling Pathways
- RNA regulation and disease
European Molecular Biology Laboratory
2015-2024
European Molecular Biology Laboratory
2015-2023
University College Dublin
2013-2019
European Molecular Biology Organization
2017
Garvan Institute of Medical Research
2011-2015
German Cancer Research Center
2015
Heidelberg University
2015
University Hospital Heidelberg
2015
The Kinghorn Cancer Centre
2015
University Hospital Cologne
2015
Abstract RNA-binding proteins (RBPs) exert a broad range of biological functions. To explore the scope RBPs across eukaryotic evolution, we determined in vivo RBP repertoire yeast Saccharomyces cerevisiae and identified 678 from additionally 729 human hepatocytic HuH-7 cells. Combined analyses these recently published data sets define core conserved to man. Conserved harbour defined repetitive motifs within disordered regions, which display striking evolutionary expansion. Only 60% 73% have...
Following the realization that eukaryotic RNA-binding proteomes are substantially larger than anticipated, we must now understand their detailed composition and dynamics. Methods such as RNA interactome capture (RIC) have begun to address this need. However, limitations of RIC been reported. Here describe enhanced (eRIC), a method based on use an LNA-modified probe, which yields numerous advantages including greater specificity increased signal-to-noise ratios compared existing methods. In...
Differentiating stem cells must coordinate their metabolism and fate trajectories. Here, we report that the catalytic activity of glycolytic enzyme Enolase 1 (ENO1) is directly regulated by RNAs leading to metabolic rewiring in mouse embryonic (mESCs). We identify RNA ligands specifically inhibit ENO1's enzymatic vitro diminish glycolysis cultured human mESCs. Pharmacological inhibition or RNAi-mediated depletion protein deacetylase SIRT2 increases acetylation enhances its binding....
Mitochondrial RNA processing is an essential step for the synthesis of components electron transport chain in all eukaryotic organisms, yet several aspects mitochondrial biogenesis and regulation are not sufficiently understood. interactome capture identified disease-relevant RNA-binding proteins (RBPs) with noncanonical architectures, including six members FASTK (FAS-activated serine/threonine kinase) family proteins. A mutation within one these newly assigned RBPs, FASTKD2, causes a rare...
Abstract System-wide approaches have unveiled an unexpected breadth of the RNA-bound proteomes cultured cells. Corresponding information regarding RNA-binding proteins (RBPs) mammalian organs is still missing, largely due to technical challenges. Here, we describe ex vivo enhanced RNA interactome capture (eRIC) characterize three different mouse organs. The resulting organ atlases encompass more than 1300 RBPs active in brain, kidney or liver. Nearly a quarter (291) these had formerly not...
The primary objective of most gene expression studies is the identification one or more signatures; lists genes whose transcriptional levels are uniquely associated with a specific biological phenotype. Whilst thousands experimentally derived signatures published, their potential value to community limited by computational inaccessibility. Gene embedded in published article figures, tables Supplementary Data, and frequently presented using non-standard probeset nomenclature. We present...
Neuroblastoma is an embryonal tumor accounting for approximately 15% of childhood cancer deaths. There exists a clinical need to identify novel therapeutic targets, particularly treatment-resistant forms neuroblastoma. Therefore, we investigated the role neuronal master regulator GSK3 in controlling neuroblastoma cell fate. We identified GSK3-mediated regulation MYC (c-MYC and MYCN) mRNA levels, which may have implications numerous MYC-driven cancers. In addition, showed that certain...
Sufficient amino acid supplies are critical for protein synthesis and, thus, cell growth and proliferation. Specialized transporters mediate exchange across membranes their regulation is homeostasis. Here, we report that the DNA- RNA-binding YBX3 regulates expression of transporters. To investigate functions YBX3, integrated proteomic transcriptomic data from cells depleted with analyses RNA binding sites to identify RNAs directly regulated by YBX3. The implicate as a distinct sets mRNAs...
Abstract RNA–protein interactions are central to cardiac function, but how activity of individual RNA-binding protein is regulated through signaling cascades in cardiomyocytes during heart failure development largely unknown. The mechanistic target rapamycin kinase a hub that controls mRNA translation cardiomyocytes; however, direct link between mTOR and proteins the has not been established. Integrative transcriptome translatome analysis revealed dependent translational upregulation RNA...
Abstract A-Raf kinase can inhibit apoptosis by binding to the proapoptotic mammalian sterile 20-like (MST2). This function relies on expression of hnRNP H, which ensures correct splicing a-raf mRNA needed produce full-length protein. Here, we showed that H and production is positively controlled c-Myc. Low c-Myc reduces switches A-Rafshort, a truncated Importantly, A-Rafshort fails regulate MST2 but retains Ras-binding domain such it functions as dominant negative mutant suppressing Ras...
Cellular stress causes multifaceted reactions to trigger adaptive responses environmental cues at all levels of the gene expression pathway. RNA-binding proteins (RBP) are key contributors stress-induced regulation RNA fate and function. Here, we uncover plasticity interactome in stressed cells, differentiating between nucleus cytoplasm. We applied enhanced capture (eRIC) analysis preceded by nucleo-cytoplasmic fractionation following arsenite-induced oxidative stress. The data reveal...
Modern omics technologies allow us to obtain global information on different types of biological networks. However, integrating these analyses into a coherent framework for comprehensive interpretation remains challenging. Here, we present conceptual that integrates protein interaction, phosphoproteomics, and transcriptomics data. Applying this method analyze HRAS signaling from subcellular compartments shows spatially defined networks contribute specific functions signaling. Changes in...
// David J. Duffy 1,7,* , Aleksandar Krstic 1,* Melinda Halasz Thomas Schwarzl 1,8,* Dirk Fey 1 Kristiina Iljin 6 Jai Prakash Mehta Kate Killick Jenny Whilde Benedetta Turriziani Saija Haapa-Paananen Vidal Matthias Fischer 5 Frank Westermann 4 Kai-Oliver Henrich Steffen Bannert Desmond G. Higgins 1,2,3 and Walter Kolch Systems Biology Ireland, University College Dublin, Belfield, Ireland 2 Conway Institute of Biomolecular & Biomedical Research, 3 School Medicine Medical Science, Division NB...
Abstract Individual-nucleotide resolution crosslinking and immunoprecipitation (iCLIP) allows the determination of sites RNA-binding proteins (RBPs) on RNAs. iCLIP is based ultraviolet light RBPs to RNA, reverse transcription high-throughput sequencing fragments terminating at site crosslinking. As a result, start are expected cluster with narrow distribution, typically representing direct interaction between RBP RNA. Here we show that for several (eIF4A3, PTB, SRSF3, SRSF4 hnRNP L),...
Retinoid therapy is widely employed in clinical oncology to differentiate malignant cells into their more benign counterparts. However, certain high-risk cohorts, such as patients with MYCN-amplified neuroblastoma, are innately resistant retinoid therapy. Therefore, we a precision medicine approach globally profile the signalling response and determine how an excess of cellular MYCN antagonises these events prevent differentiation confer resistance. We applied RNA sequencing (RNA-seq)...
// David J. Duffy 1, 7, * , Aleksandar Krstic Thomas Schwarzl 8 Melinda Halasz 1 Kristiina Iljin 6 Dirk Fey Bridget Haley Jenny Whilde Saija Haapa-Paananen Vidal Matthias Fischer 5 Frank Westermann 4 Kai-Oliver Henrich Steffen Bannert Desmond G. Higgins 2, 3 Walter Kolch Systems Biology Ireland, University College Dublin, Belfield, Ireland 2 Conway Institute of Biomolecular and Biomedical Research, School Medicine, Division NB Genomics, German Cancer Research Center (DKFZ), Heidelberg,...
RNA-binding proteins (RBPs) control critical aspects of cardiomyocyte function, but the repertoire active RBPs in cardiomyocytes during growth response is largely unknown. We define healthy and diseased at a system-wide level by RNA interactome capture. This identifies 67 cardiomyocyte-specific RBPs, including several contractile proteins. Furthermore, we identify cytoplasmic polyadenylation element-binding protein 4 (Cpeb4) as dynamic RBP, regulating cardiac both vitro vivo. mRNAs bound to...
Enhanced crosslinking and immunoprecipitation (eCLIP) sequencing is a method for transcriptome-wide detection of binding sites RNA-binding proteins (RBPs). However, identified crosslink can deviate from experimentally established functional elements even well-studied RBPs. Current peak-calling strategies result in low replication high false positive rates. Here, we present the R/Bioconductor package DEWSeq that makes use replicate information size-matched input controls. We benchmarked on...
Uncontrolled cell cycle entry, resulting from deregulated CDK-RB1-E2F pathway activity, is a crucial determinant of neuroblastoma malignancy. Here we identify neuroblastoma-suppressive functions the p19-INK4d CDK inhibitor and uncover mechanisms its repression in high-risk neuroblastomas. Reduced expression was associated with poor event-free overall survival risk factors including amplified MYCN set 478 primary High repressed mRNA protein levels different models conditional expression....