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Jantsch Michael

Matthias Schaefer, Utkarsh Kapoor, Michael F Jantsch
The discovery of mechanisms that alter genetic information via RNA editing or introducing covalent RNA modifications points towards a complexity in gene expression that challenges long-standing concepts. Understanding the biology of RNA modifications represents one of the next frontiers in molecular biology. To this date, over 130 different RNA modifications have been identified, and improved mass spectrometry approaches are still adding to this list. However, only recently has it been possible to map selected RNA modifications at single-nucleotide resolution, which has created a number of exciting hypotheses about the biological function of RNA modifications, culminating in the proposition of the 'epitranscriptome'...
May 2017: Open Biology
Andrea Barta, Michael F Jantsch
No abstract text is available yet for this article.
May 4, 2017: RNA Biology
Christoph Kopp, Christian Beyer, Peter Linz, Anke Dahlmann, Matthias Hammon, Jonathan Jantsch, Patrick Neubert, Daniela Rosenhauer, Dominik N Müller, Alexander Cavallaro, Kai-Uwe Eckardt, Georg Schett, Friedrich C Luft, Michael Uder, Jörg H W Distler, Jens Titze
No abstract text is available yet for this article.
April 1, 2017: Rheumatology
Prajakta Bajad, Michael F Jantsch, Liam Keegan, Mary O'Connell
Adenosine deaminases acting on RNA (ADARs) are zinc-containing enzymes that deaminate adenosine bases to inosines within dsRNA regions in transcripts. In short, structured dsRNA hairpins individual adenosine bases may be targeted specifically and edited with up to one hundred percent efficiency, leading to the production of alternative protein variants. However, the majority of editing events occur within longer stretches of dsRNA formed by pairing of repetitive sequences. Here, many different adenosine bases are potential targets but editing efficiency is usually much lower...
March 27, 2017: RNA Biology
Aparna Anantharaman, Vidisha Tripathi, Abid Khan, Je-Hyun Yoon, Deepak K Singh, Omid Gholamalamdari, Shuomeng Guang, Johan Ohlson, Helene Wahlstedt, Marie Öhman, Michael F Jantsch, Nicholas K Conrad, Jian Ma, Myriam Gorospe, Supriya G Prasanth, Kannanganattu V Prasanth
Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within RNA sequences, mostly in the introns and UTRs (un-translated regions). The significance of editing within non-coding regions of RNA is poorly understood. Here, we demonstrate that association of ADAR2 with RNA stabilizes a subset of transcripts. ADAR2 interacts with and edits the 3΄UTR of nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). In absence of ADAR2, the abundance and half-life of Ctn RNA are significantly reduced...
April 20, 2017: Nucleic Acids Research
Christoph Kopp, Christian Beyer, Peter Linz, Anke Dahlmann, Matthias Hammon, Jonathan Jantsch, Patrick Neubert, Daniela Rosenhauer, Dominik N Müller, Alexander Cavallaro, Kai-Uwe Eckardt, Georg Schett, Friedrich C Luft, Michael Uder, Jörg H W Distler, Jens Titze
Objective.: Skin fibrosis is the predominant feature of SSc and arises from excessive extracellular matrix deposition. Glycosaminoglycans are macromolecules of the extracellular matrix, which facilitate Na + accumulation in the skin. We used 23 Na-MRI to quantify Na + in skin. We hypothesized that skin Na + might accumulate in SSc and might be a biomarker for skin fibrosis. Methods.: In this observational case-control study, skin Na + was determined by 23 Na-MRI using a Na + volume coil in 12 patients with diffuse cutaneous SSc and in 21 control subjects...
April 1, 2017: Rheumatology
Mansoureh Tajaddod, Andrea Tanzer, Konstantin Licht, Michael T Wolfinger, Stefan Badelt, Florian Huber, Oliver Pusch, Sandy Schopoff, Michael Janisiw, Ivo Hofacker, Michael F Jantsch
BACKGROUND: Short interspersed elements (SINEs) represent the most abundant group of non-long-terminal repeat transposable elements in mammalian genomes. In primates, Alu elements are the most prominent and homogenous representatives of SINEs. Due to their frequent insertion within or close to coding regions, SINEs have been suggested to play a crucial role during genome evolution. Moreover, Alu elements within mRNAs have also been reported to control gene expression at different levels...
October 25, 2016: Genome Biology
Aparna Anantharaman, Mahdieh Jadaliha, Vidisha Tripathi, Shinichi Nakagawa, Tetsuro Hirose, Michael F Jantsch, Supriya G Prasanth, Kannanganattu V Prasanth
Paraspeckles are sub-nuclear domains that are nucleated by long noncoding RNA Neat1. While interaction of protein components of paraspeckles and Neat1 is understood, there is limited information on the interaction of non-structural RNA components with paraspeckles. Here, by varying paraspeckle number and size, we investigate how paraspeckles influence the nuclear organization of their non-structural RNA component Ctn RNA. Our results show that Ctn RNA remains nuclear-retained in the absence of intact paraspeckles, suggesting that they do not regulate nuclear retention of Ctn RNA...
September 26, 2016: Scientific Reports
Konstantin Licht, Utkarsh Kapoor, Elisa Mayrhofer, Michael F Jantsch
Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon-intron basepairing, mRNA splicing efficiency should affect editing levels. Moreover, splicing rates affect nuclear retention and will therefore also influence the exposure of pre-mRNAs to the editing-competent nuclear environment. Here, we systematically test the influence of splice rates on RNA-editing using reporter genes but also endogenous substrates...
July 27, 2016: Nucleic Acids Research
Anahita Daryabeigi, Alexander Woglar, Antoine Baudrimont, Nicola Silva, Dimitra Paouneskou, Cornelia Vesely, Manuel Rauter, Alexandra Penkner, Michael Jantsch, Verena Jantsch
SUN (Sad1 and UNC-84) and KASH (Klarsicht, ANC-1, and Syne homology) proteins are constituents of the inner and outer nuclear membranes. They interact in the perinuclear space via C-terminal SUN-KASH domains to form the linker of nucleoskeleton and cytoskeleton (LINC) complex thereby bridging the nuclear envelope. LINC complexes mediate numerous biological processes by connecting chromatin with the cytoplasmic force-generating machinery. Here we show that the coiled-coil domains of SUN-1 are required for oligomerization and retention of the protein in the nuclear envelope, especially at later stages of female gametogenesis...
June 2016: Genetics
Konstantin Licht, Michael F Jantsch
Advances in next-generation sequencing and mass spectrometry have revealed widespread messenger RNA modifications and RNA editing, with dramatic effects on mammalian transcriptomes. Factors introducing, deleting, or interpreting specific modifications have been identified, and analogous with epigenetic terminology, have been designated "writers," "erasers," and "readers." Such modifications in the transcriptome are referred to as epitranscriptomic changes and represent a fascinating new layer of gene expression regulation that has only recently been appreciated...
April 11, 2016: Journal of Cell Biology
Mansoureh Tajaddod, Michael F Jantsch, Konstantin Licht
Adenosine to inosine editing (A to I editing) is a cotranscriptional process that contributes to transcriptome complexity by deamination of adenosines to inosines. Initially, the impact of A to I editing has been described for coding targets in the nervous system. Here, A to I editing leads to recoding and changes of single amino acids since inosine is normally interpreted as guanosine by cellular machines. However, more recently, new roles for A to I editing have emerged: Editing was shown to influence splicing and is found massively in Alu elements...
March 2016: Chromosoma
Jonas Jennewein, Jasmin Matuszak, Steffi Walter, Boas Felmy, Kathrin Gendera, Valentin Schatz, Monika Nowottny, Gregor Liebsch, Michael Hensel, Wolf-Dietrich Hardt, Roman G Gerlach, Jonathan Jantsch
In Salmonella infection, the Salmonella pathogenicity island-2 (SPI-2)-encoded type three secretion system (T3SS2) is of key importance for systemic disease and survival in host cells. For instance, in the streptomycin-pretreated mouse model SPI-2-dependent Salmonella replication in lamina propria CD11c(-)CXCR1(-) monocytic phagocytes/macrophages (MΦ) is required for the development of colitis. In addition, containment of intracellular Salmonella in the gut critically depends on the antimicrobial effects of the phagocyte NADPH oxidase (PHOX), and possibly type 2 nitric oxide synthase (NOS2)...
December 2015: Cellular Microbiology
Jonathan Jantsch, Valentin Schatz, Diana Friedrich, Agnes Schröder, Christoph Kopp, Isabel Siegert, Andreas Maronna, David Wendelborn, Peter Linz, Katrina J Binger, Matthias Gebhardt, Matthias Heinig, Patrick Neubert, Fabian Fischer, Stefan Teufel, Jean-Pierre David, Clemens Neufert, Alexander Cavallaro, Natalia Rakova, Christoph Küper, Franz-Xaver Beck, Wolfgang Neuhofer, Dominik N Muller, Gerold Schuler, Michael Uder, Christian Bogdan, Friedrich C Luft, Jens Titze
Immune cells regulate a hypertonic microenvironment in the skin; however, the biological advantage of increased skin Na(+) concentrations is unknown. We found that Na(+) accumulated at the site of bacterial skin infections in humans and in mice. We used the protozoan parasite Leishmania major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na(+) storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase (p38/MAPK)-dependent nuclear factor of activated T cells 5 (NFAT5) activation...
March 3, 2015: Cell Metabolism
Niamh M Mannion, Sam M Greenwood, Robert Young, Sarah Cox, James Brindle, David Read, Christoffer Nellåker, Cornelia Vesely, Chris P Ponting, Paul J McLaughlin, Michael F Jantsch, Julia Dorin, Ian R Adams, A D J Scadden, Marie Ohman, Liam P Keegan, Mary A O'Connell
The ADAR RNA-editing enzymes deaminate adenosine bases to inosines in cellular RNAs. Aberrant interferon expression occurs in patients in whom ADAR1 mutations cause Aicardi-Goutières syndrome (AGS) or dystonia arising from striatal neurodegeneration. Adar1 mutant mouse embryos show aberrant interferon induction and die by embryonic day E12.5. We demonstrate that Adar1 embryonic lethality is rescued to live birth in Adar1; Mavs double mutants in which the antiviral interferon induction response to cytoplasmic double-stranded RNA (dsRNA) is prevented...
November 20, 2014: Cell Reports
Cornelia Vesely, Stefanie Tauber, Fritz J Sedlazeck, Mansoureh Tajaddod, Arndt von Haeseler, Michael F Jantsch
Adenosine deaminases that act on RNA (ADARs) deaminate adenosines to inosines in double-stranded RNAs including miRNA precursors. A to I editing is widespread and required for normal life. By comparing deep sequencing data of brain miRNAs from wild-type and ADAR2 deficient mouse strains, we detect editing sites and altered miRNA processing at high sensitivity. We detect 48 novel editing events in miRNAs. Some editing events reach frequencies of up to 80%. About half of all editing events depend on ADAR2 while some miRNAs are preferentially edited by ADAR1...
October 29, 2014: Nucleic Acids Research
Dominik Muggenhumer, Cornelia Vesely, Simon Nimpf, Nan Tian, Jin Yongfeng, Michael F Jantsch
MicroRNAs (miRNAs) are ∼21-nucleotide-long, single-stranded noncoding RNAs that regulate gene expression. Biogenesis of miRNAs is mediated by the two RNase III-like enzymes, Drosha and Dicer. Here we study miRNA biogenesis during maturation of Xenopus oocytes to eggs using microinjection of pri-miRNAs. We show that processing of exogenous and endogenous primary miRNAs (pri-miRNAs) is strongly enhanced upon maturation of oocytes to eggs. Overexpression of cloned Xenopus Drosha in oocytes, however, boosts pri-miRNA processing dramatically, indicating that Drosha is a rate-limiting factor in Xenopus oocytes...
July 1, 2014: Molecular Biology of the Cell
Pierre Barraud, Silpi Banerjee, Weaam I Mohamed, Michael F Jantsch, Frédéric H-T Allain
The human RNA-editing enzyme adenosine deaminase acting on RNA (ADAR1) carries a unique nuclear localization signal (NLS) that overlaps one of its double-stranded RNA-binding domains (dsRBDs). This dsRBD-NLS is recognized by the nuclear import receptor transportin 1 (Trn1; also called karyopherin-β2) in an RNA-sensitive manner. Most Trn1 cargos bear a well-characterized proline-tyrosine-NLS, which is missing from the dsRBD-NLS. Here, we report the structure of the dsRBD-NLS, which reveals an unusual dsRBD fold extended by an additional N-terminal α-helix that brings the N- and C-terminal flanking regions in close proximity...
May 6, 2014: Proceedings of the National Academy of Sciences of the United States of America
Maja Stulić, Michael F Jantsch
RNA editing by ADARs can change the coding potential of protein-coding mRNAs. So far, this type of RNA editing has mainly been shown to affect RNAs expressed in the nervous system with much lower editing levels being observed in other tissues. The actin crosslinking proteins filamin α and filamin β are widely expressed in most tissues. The mRNAs encoding either protein are edited at the same position leading to a conserved Q to R exchange in both proteins. Using bar-coded next generation sequencing, we show that editing of filamin α is most abundant in the gastrointestinal tract and only to a lesser extent in the nervous system...
October 2013: RNA Biology
Helge Wiig, Agnes Schröder, Wolfgang Neuhofer, Jonathan Jantsch, Christoph Kopp, Tine V Karlsen, Michael Boschmann, Jennifer Goss, Maija Bry, Natalia Rakova, Anke Dahlmann, Sven Brenner, Olav Tenstad, Harri Nurmi, Eero Mervaala, Hubertus Wagner, Franz-Xaver Beck, Dominik N Müller, Dontscho Kerjaschki, Friedrich C Luft, David G Harrison, Kari Alitalo, Jens Titze
The skin interstitium sequesters excess Na+ and Cl- in salt-sensitive hypertension. Mononuclear phagocyte system (MPS) cells are recruited to the skin, sense the hypertonic electrolyte accumulation in skin, and activate the tonicity-responsive enhancer-binding protein (TONEBP, also known as NFAT5) to initiate expression and secretion of VEGFC, which enhances electrolyte clearance via cutaneous lymph vessels and increases eNOS expression in blood vessels. It is unclear whether this local MPS response to osmotic stress is important to systemic blood pressure control...
July 2013: Journal of Clinical Investigation
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