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Violeta Rayon-Estrada, Dewi Harjanto, Claire E Hamilton, Yamina A Berchiche, Emily Conn Gantman, Thomas P Sakmar, Karen Bulloch, Khatuna Gagnidze, Sheila Harroch, Bruce S McEwen, F Nina Papavasiliou
Epitranscriptomics refers to posttranscriptional alterations on an mRNA sequence that are dynamic and reproducible, and affect gene expression in a similar way to epigenetic modifications. However, the functional relevance of those modifications for the transcript, the cell, and the organism remain poorly understood. Here, we focus on RNA editing and show that Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-1 (APOBEC1), together with its cofactor RBM47, mediates robust editing in different tissues...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
Matjaz Rokavec, Markus Kaller, David Horst, Heiko Hermeking
Epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and metastasis. A comprehensive, bioinformatics analysis of CCLE and TCGA datasets of seven tumor types allowed us to identify a novel pan-cancer EMT-associated gene expression signature consisting of 16 epithelial and 4 mesenchymal state-associated mRNAs. Among the identified epithelial cell state-associated factors, down-regulation of the RBM47 (RNA binding motif protein 47) mRNA displayed the most significant association with metastasis and poor survival in multiple cohorts of colorectal cancer (CRC) patients...
July 5, 2017: Scientific Reports
Praveen Surendran, Fotios Drenos, Robin Young, Helen Warren, James P Cook, Alisa K Manning, Niels Grarup, Xueling Sim, Daniel R Barnes, Kate Witkowska, James R Staley, Vinicius Tragante, Taru Tukiainen, Hanieh Yaghootkar, Nicholas Masca, Daniel F Freitag, Teresa Ferreira, Olga Giannakopoulou, Andrew Tinker, Magdalena Harakalova, Evelin Mihailov, Chunyu Liu, Aldi T Kraja, Sune Fallgaard Nielsen, Asif Rasheed, Maria Samuel, Wei Zhao, Lori L Bonnycastle, Anne U Jackson, Narisu Narisu, Amy J Swift, Lorraine Southam, Jonathan Marten, Jeroen R Huyghe, Alena Stančáková, Cristiano Fava, Therese Ohlsson, Angela Matchan, Kathleen E Stirrups, Jette Bork-Jensen, Anette P Gjesing, Jukka Kontto, Markus Perola, Susan Shaw-Hawkins, Aki S Havulinna, He Zhang, Louise A Donnelly, Christopher J Groves, N William Rayner, Matt J Neville, Neil R Robertson, Andrianos M Yiorkas, Karl-Heinz Herzig, Eero Kajantie, Weihua Zhang, Sara M Willems, Lars Lannfelt, Giovanni Malerba, Nicole Soranzo, Elisabetta Trabetti, Niek Verweij, Evangelos Evangelou, Alireza Moayyeri, Anne-Claire Vergnaud, Christopher P Nelson, Alaitz Poveda, Tibor V Varga, Muriel Caslake, Anton Jm de Craen, Stella Trompet, Jian'an Luan, Robert A Scott, Sarah E Harris, David Cm Liewald, Riccardo Marioni, Cristina Menni, Aliki-Eleni Farmaki, Göran Hallmans, Frida Renström, Jennifer E Huffman, Maija Hassinen, Stephen Burgess, Ramachandran S Vasan, Janine F Felix, Maria Uria-Nickelsen, Anders Malarstig, Dermot F Reily, Maarten Hoek, Thomas Vogt, Honghuang Lin, Wolfgang Lieb, Matthew Traylor, Hugh F Markus, Heather M Highland, Anne E Justice, Eirini Marouli, Jaana Lindström, Matti Uusitupa, Pirjo Komulainen, Timo A Lakka, Rainer Rauramaa, Ozren Polasek, Igor Rudan, Olov Rolandsson, Paul W Franks, George Dedoussis, Timothy D Spector, Pekka Jousilahti, Satu Männistö, Ian J Deary, John M Starr, Claudia Langenberg, Nick J Wareham, Morris J Brown, Anna F Dominiczak, John M Connell, J Wouter Jukema, Naveed Sattar, Ian Ford, Chris J Packard, Tõnu Esko, Reedik Mägi, Andres Metspalu, Rudolf A de Boer, Peter van der Meer, Pim van der Harst, Giovanni Gambaro, Erik Ingelsson, Lars Lind, Paul Iw de Bakker, Mattijs E Numans, Ivan Brandslund, Cramer Christensen, Eva Rb Petersen, Eeva Korpi-Hyövälti, Heikki Oksa, John C Chambers, Jaspal S Kooner, Alexandra If Blakemore, Steve Franks, Marjo-Riitta Jarvelin, Lise L Husemoen, Allan Linneberg, Tea Skaaby, Betina Thuesen, Fredrik Karpe, Jaakko Tuomilehto, Alex Sf Doney, Andrew D Morris, Colin Na Palmer, Oddgeir Lingaas Holmen, Kristian Hveem, Cristen J Willer, Tiinamaija Tuomi, Leif Groop, AnneMari Käräjämäki, Aarno Palotie, Samuli Ripatti, Veikko Salomaa, Dewan S Alam, Abdulla Al Shafi Majumder, Emanuele Di Angelantonio, Rajiv Chowdhury, Mark I McCarthy, Neil Poulter, Alice V Stanton, Peter Sever, Philippe Amouyel, Dominique Arveiler, Stefan Blankenberg, Jean Ferrières, Frank Kee, Kari Kuulasmaa, Martina Müller-Nurasyid, Giovanni Veronesi, Jarmo Virtamo, Panos Deloukas, Paul Elliott, Eleftheria Zeggini, Sekar Kathiresan, Olle Melander, Johanna Kuusisto, Markku Laakso, Sandosh Padmanabhan, David Porteous, Caroline Hayward, Generation Scotland, Francis S Collins, Karen L Mohlke, Torben Hansen, Oluf Pedersen, Michael Boehnke, Heather M Stringham, Philippe Frossard, Christopher Newton-Cheh, Martin D Tobin, Børge Grønne Nordestgaard, Mark J Caulfield, Anubha Mahajan, Andrew P Morris, Maciej Tomaszewski, Nilesh J Samani, Danish Saleheen, Folkert W Asselbergs, Cecilia M Lindgren, John Danesh, Louise V Wain, Adam S Butterworth, Joanna Mm Howson, Patricia B Munroe
High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1...
October 2016: Nature Genetics
Benjamin Cieply, Juw Won Park, Angela Nakauka-Ddamba, Thomas W Bebee, Yang Guo, Xuequn Shang, Christopher J Lengner, Yi Xing, Russ P Carstens
Alternative splicing (AS) plays a critical role in cell fate transitions, development, and disease. Recent studies have shown that AS also influences pluripotency and somatic cell reprogramming. We profiled transcriptome-wide AS changes that occur during reprogramming of fibroblasts to pluripotency. This analysis revealed distinct phases of AS, including a splicing program that is unique to transgene-independent induced pluripotent stem cells (iPSCs). Changes in the expression of AS factors Zcchc24, Esrp1, Mbnl1/2, and Rbm47 were demonstrated to contribute to phase-specific AS...
April 12, 2016: Cell Reports
Yueqin Yang, Juw Won Park, Thomas W Bebee, Claude C Warzecha, Yang Guo, Xuequn Shang, Yi Xing, Russ P Carstens
The epithelial-to-mesenchymal transition (EMT) is an essential biological process during embryonic development that is also implicated in cancer metastasis. While the transcriptional regulation of EMT has been well studied, the role of alternative splicing (AS) regulation in EMT remains relatively uncharacterized. We previously showed that the epithelial cell-type-specific proteins epithelial splicing regulatory proteins 1 (ESRP1) and ESRP2 are important for the regulation of many AS events that are altered during EMT...
June 1, 2016: Molecular and Cellular Biology
T Sakurai, K Isogaya, S Sakai, M Morikawa, Y Morishita, S Ehata, K Miyazono, D Koinuma
RNA-binding proteins provide a new layer of posttranscriptional regulation of RNA during cancer progression. We identified RNA-binding motif protein 47 (RBM47) as a target gene of transforming growth factor (TGF)-β in mammary gland epithelial cells (NMuMG cells) that have undergone the epithelial-to-mesenchymal transition. TGF-β repressed RBM47 expression in NMuMG cells and lung cancer cell lines. Expression of RBM47 correlated with good prognosis in patients with lung, breast and gastric cancer. RBM47 suppressed the expression of cell metabolism-related genes, which were the direct targets of nuclear factor erythroid 2-related factor 2 (Nrf2; also known as NFE2L2)...
September 22, 2016: Oncogene
Nicolas Fossat, Patrick P L Tam
Cytidine (C) to Uridine (U) RNA editing is a post-trancriptional modification that until recently was known to only affect Apolipoprotein b (Apob) RNA and minimally require 2 components of the C to U editosome, the deaminase APOBEC1 and the RNA-binding protein A1CF. Our latest work has identified a novel RNA-binding protein, RBM47, as a core component of the editosome, which can substitute A1CF for the editing of ApoB mRNA. In addition, new RNA species that are subjected to C to U editing have been identified...
2014: RNA Biology
Nicolas Fossat, Karin Tourle, Tania Radziewic, Kristen Barratt, Doreen Liebhold, Joshua B Studdert, Melinda Power, Vanessa Jones, David A F Loebel, Patrick P L Tam
Cytidine (C) to Uridine (U) RNA editing is a post-transcriptional modification that is accomplished by the deaminase APOBEC1 and its partnership with the RNA-binding protein A1CF. We identify and characterise here a novel RNA-binding protein, RBM47, that interacts with APOBEC1 and A1CF and is expressed in tissues where C to U RNA editing occurs. RBM47 can substitute for A1CF and is necessary and sufficient for APOBEC1-mediated editing in vitro. Editing is further impaired in Rbm47-deficient mutant mice. These findings suggest that RBM47 and APOBEC1 constitute the basic machinery for C to U RNA editing...
August 2014: EMBO Reports
Sakari Vanharanta, Christina B Marney, Weiping Shu, Manuel Valiente, Yilong Zou, Aldo Mele, Robert B Darnell, Joan Massagué
The mechanisms through which cancer cells lock in altered transcriptional programs in support of metastasis remain largely unknown. Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we identified RNA binding motif protein 47 (RBM47) as a suppressor of breast cancer progression and metastasis. RBM47 inhibited breast cancer re-initiation and growth in experimental models. Transcriptome-wide HITS-CLIP analysis revealed widespread RBM47 binding to mRNAs, most prominently in introns and 3'UTRs...
June 4, 2014: ELife
Rui Guan, Suzan El-Rass, David Spillane, Simon Lam, Yuodong Wang, Jing Wu, Zhuchu Chen, Anan Wang, Zhengping Jia, Armand Keating, Jim Hu, Xiao-Yan Wen
BACKGROUND: Vertebrate trunk induction requires inhibition of bone morphogenetic protein (BMP) signaling, whereas vertebrate head induction requires concerted inhibition of both Wnt and BMP signaling. RNA binding proteins play diverse roles in embryonic development and their roles in vertebrate head development remain to be elucidated. RESULTS: We first characterized the human RBM47 as an RNA binding protein that specifically binds RNA but not single-stranded DNA...
December 2013: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Meghdad Yeganeh, Ehsan Seyedjafari, Farnaz Akbari Kamrani, Nasser Ghaemi
Embryonic stem cells (ES cells) are pluripotent cells capable for self-renewal and to differentiate to all cell types. Finding the molecular mechanisms responsible for these unique characteristics of ES cells is important. RNA-binding proteins play important roles in post-transcriptional gene regulation by binding to specific mRNA targets. In this study, we investigated the targets of RNA-binding protein Rbm47 in mouse ES cells. Overexpression of HA epitope-tagged Rbm47 in mouse ES cells followed by RNA-binding protein immunoprecipitation, and then RT-PCR analysis of co-immunoprecipitated RNA showed that Rbm47 binds to Nanog transcript in mouse ES cells and doesn't bind to Sox2 and Oct4 transcripts in these cells...
July 2013: Molecular Biology Reports
Bo-Zhi Chen, Sung-Liang Yu, Sher Singh, Li-Pin Kao, Zong-Yun Tsai, Pan-Chyr Yang, Bai-Hsiun Chen, Steven Shoei-Lung Li
Type 1 diabetes is an autoimmune destruction of pancreatic islet beta cell disease, making it important to find a new alternative source of the islet beta cells to replace the damaged cells. hES (human embryonic stem) cells possess unlimited self-renewal and pluripotency and thus have the potential to provide an unlimited supply of different cell types for tissue replacement. The hES-T3 cells with normal female karyotype were first differentiated into EBs (embryoid bodies) and then induced to generate the T3pi (pancreatic islet-like cell clusters derived from T3 cells), which expressed pancreatic islet cell-specific markers of insulin, glucagon and somatostatin...
January 2011: Cell Biology International
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