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JOURNAL ARTICLE
Niko Popitsch, Christian D Huber, Ilana Buchumenski, Eli Eisenberg, Michael Jantsch, Arndt von Haeseler, Miguel Gallach
In animals, the most common type of RNA editing is the deamination of adenosines (A) into inosines (I). Because inosines base-pair with cytosines (C), they are interpreted as guanosines (G) by the cellular machinery and genomically encoded G alleles at edited sites mimic the function of edited RNAs. The contribution of this hardwiring effect on genome evolution remains obscure. We looked for population genomics signatures of adaptive evolution associated with A-to-I RNA edited sites in humans and Drosophila melanogaster...
March 7, 2020: Genome Biology and Evolution
#22
JOURNAL ARTICLE
Prajakta Bajad, Florian Ebner, Fabian Amman, Brigitta Szabó, Utkarsh Kapoor, Greeshma Manjali, Alwine Hildebrandt, Michael P Janisiw, Michael F Jantsch
The RNA-editing protein ADAR is essential for early development in the mouse. Genetic evidence suggests that A to I editing marks endogenous RNAs as 'self'. Today, different Adar knockout alleles have been generated that show a common phenotype of apoptosis, liver disintegration, elevated immune response and lethality at E12.5. All the Adar knockout alleles can be rescued by a concomitant deletion of the innate immunity genes Mavs or Ifih1 (MDA5), albeit to different extents. This suggests multiple functions of ADAR...
January 20, 2020: Nucleic Acids Research
#23
REVIEW
Mamta Jain, Michael F Jantsch, Konstantin Licht
Adenosine-to-inosine (A-to-I) editing of RNA leads to deamination of adenosine to inosine. Inosine is interpreted as guanosine by the cellular machinery, thus altering the coding, folding, splicing, or transport of transcripts. A-to-I editing is tightly regulated. Altered editing has severe consequences for human health and can cause interferonopathies, neurological disorders, and cardiovascular disease, as well as impacting on cancer progression. ADAR1-mediated RNA editing plays an important role in antiviral immunity and is essential for distinguishing between endogenous and viral RNA, thereby preventing autoimmune disorders...
December 2019: Trends in Genetics: TIG
#24
EDITORIAL
Verena Jantsch, Michael Jantsch
Funding research is a challenge faced by most scientists around the world. Genome Biology has invited four scientists based in three different countries to share their own experience and opinions regarding funding, the difficulties young scientists must overcome, and how the process of securing funding can be improved. In this part, Verena and Michael Jantsch describe their thoughts on funding research from a European perspective.
August 28, 2019: Genome Biology
#25
REVIEW
Marco Niello, Daniela Cintulova, Eva Hellsberg, Kathrin Jäntsch, Marion Holy, Leila H Ayatollahi, Nicholas V Cozzi, Michael Freissmuth, Walter Sandtner, Gerhard F Ecker, Marko D Mihovilovic, Harald H Sitte
The transporters for dopamine (DAT) and serotonin (SERT) are important targets in the treatment of psychiatric disorders including major depression, anxiety and attention-deficit hyperactivity disorder. Drugs acting at these transporters can act as inhibitors or as releasers. In addition, it has been recently appreciated that some compounds are less efficacious releasers than amphetamine. Thus, they are classified as partial releasers. Compounds can act on both SERT and DAT or display exquisite selectivity for either SERT or DAT, but the structural basis for selectivity is poorly understood...
April 24, 2019: Neuropharmacology
#26
EDITORIAL
Michael F Jantsch, Matthias R Schaefer
No abstract text is available yet for this article.
March 1, 2019: Methods: a Companion to Methods in Enzymology
#27
JOURNAL ARTICLE
Marie Fablet, Angelo Jacquet, Rita Rebollo, Annabelle Haudry, Carine Rey, Judit Salces-Ortiz, Prajakta Bajad, Nelly Burlet, Michael F Jantsch, Maria Pilar García Guerreiro, Cristina Vieira
All genomes contain repeated sequences that are known as transposable elements (TEs). Among these are endogenous retroviruses (ERVs), which are sequences similar to retroviruses and are transmitted across generations from parent to progeny. These sequences are controlled in genomes through epigenetic mechanisms. At the center of the epigenetic control of TEs are small interfering RNAs of the piRNA class, which trigger heterochromatinization of TE sequences. The tirant ERV of Drosophila simulans displays intra-specific variability in copy numbers, insertion sites, and transcription levels, providing us with a well-suited model to study the dynamic relationship between a TE family and the host genome through epigenetic mechanisms...
January 18, 2019: G3: Genes—Genomes—Genetics
#28
JOURNAL ARTICLE
Konstantin Licht, Markus Hartl, Fabian Amman, Dorothea Anrather, Michael P Janisiw, Michael F Jantsch
RNA modifications are present in all classes of RNAs. They control the fate of mRNAs by affecting their processing, translation, or stability. Inosine is a particularly widespread modification in metazoan mRNA arising from deamination of adenosine catalyzed by the RNA-targeting adenosine deaminases ADAR1 or ADAR2. Inosine is commonly thought to be interpreted as guanosine by cellular machines and during translation. Here, we systematically test ribosomal decoding using mass spectrometry. We show that while inosine is primarily interpreted as guanosine it can also be decoded as adenosine, and rarely even as uracil...
November 20, 2018: Nucleic Acids Research
#29
JOURNAL ARTICLE
Mamta Jain, Tomer D Mann, Maja Stulić, Shailaja P Rao, Andrijana Kirsch, Dieter Pullirsch, Xué Strobl, Claus Rath, Lukas Reissig, Kristin Moreth, Tanja Klein-Rodewald, Raffi Bekeredjian, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, Eleonore Pablik, Laura Cimatti, David Martin, Jelena Zinnanti, Wolfgang F Graier, Maria Sibilia, Saša Frank, Erez Y Levanon, Michael F Jantsch
Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases...
October 1, 2018: EMBO Journal
#30
JOURNAL ARTICLE
Philipp Czermak, Fabian Amman, Michael F Jantsch, Laura Cimatti
Adenosine to inosine RNA editing in protein-coding messenger RNAs (mRNAs) potentially leads to changes in the amino acid composition of the encoded proteins. The mRNAs encoding the ubiquitously expressed actin-crosslinking proteins Filamin A and Filamin B undergo RNA editing leading to a highly conserved glutamine to arginine exchange at the identical position in either protein. Here, by targeted amplicon sequencing we analysed the RNA editing of Filamin B across several mouse tissues during post-natal development...
2018: RNA Biology
#31
JOURNAL ARTICLE
Michael F Jantsch, Alessandro Quattrone, Mary O'Connell, Mark Helm, Michaela Frye, Manuel Macias-Gonzales, Marie Ohman, Stefan Ameres, Luc Willems, Francois Fuks, Anastasis Oulas, Stepanka Vanacova, Henrik Nielsen, Cecile Bousquet-Antonelli, Yuri Motorin, Jean-Yves Roignant, Nikolaos Balatsos, Andras Dinnyes, Pavel Baranov, Vincent Kelly, Ayelet Lamm, Gideon Rechavi, Mattia Pelizzola, Janis Liepins, Irina Holodnuka Kholodnyuk, Vanessa Zammit, Duncan Ayers, Finn Drablos, John Arne Dahl, Janusz Bujnicki, Carmen Jeronimo, Raquel Almeida, Monica Neagu, Marieta Costache, Jasna Bankovic, Bojana Banovic, Jan Kyselovic, Luis Miguel Valor, Stefan Selbert, Pinar Pir, Turan Demircan, Victoria Cowling, Matthias Schäfer, Walter Rossmanith, Denis Lafontaine, Alexandre David, Clement Carre, Frank Lyko, Raffael Schaffrath, Schraga Schwartz, Andre Verdel, Arne Klungland, Elzbieta Purta, Gordana Timotijevic, Fernando Cardona, Alberto Davalos, Ester Ballana, Donal O Carroll, Jernej Ule, Rupert Fray
The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research...
2018: RNA Biology
#32
JOURNAL ARTICLE
Laura Avogaro, Emmanuelle Querido, Myriam Dalachi, Michael F Jantsch, Pascal Chartrand, Emilio Cusanelli
Telomeres cap the ends of eukaryotic chromosomes, protecting them from degradation and erroneous recombination events which may lead to genome instability. Telomeres are transcribed giving rise to telomeric repeat-containing RNAs, called TERRA. The TERRA long noncoding RNAs have been proposed to play important roles in telomere biology, including heterochromatin formation and telomere length homeostasis. While TERRA RNAs are predominantly nuclear and localize at telomeres, little is known about the dynamics and function of TERRA molecules expressed from individual telomeres...
2018: RNA Biology
#33
JOURNAL ARTICLE
Xianyi Meng, Bettina Grötsch, Yubin Luo, Karl Xaver Knaup, Michael Sean Wiesener, Xiao-Xiang Chen, Jonathan Jantsch, Simon Fillatreau, Georg Schett, Aline Bozec
Hypoxia-inducible factors (HIFs) are key elements for controlling immune cell metabolism and functions. While HIFs are known to be involved in T cells and macrophages activation, their functions in B lymphocytes are poorly defined. Here, we show that hypoxia-inducible factor-1α (HIF-1α) contributes to IL-10 production by B cells. HIF-1α regulates IL-10 expression, and HIF-1α-dependent glycolysis facilitates CD1dhi CD5+ B cells expansion. Mice with B cell-specific deletion of Hif1a have reduced number of IL-10-producing B cells, which result in exacerbated collagen-induced arthritis and experimental autoimmune encephalomyelitis...
January 17, 2018: Nature Communications
#34
JOURNAL ARTICLE
Nicola Wilck, Mariana G Matus, Sean M Kearney, Scott W Olesen, Kristoffer Forslund, Hendrik Bartolomaeus, Stefanie Haase, Anja Mähler, András Balogh, Lajos Markó, Olga Vvedenskaya, Friedrich H Kleiner, Dmitry Tsvetkov, Lars Klug, Paul I Costea, Shinichi Sunagawa, Lisa Maier, Natalia Rakova, Valentin Schatz, Patrick Neubert, Christian Frätzer, Alexander Krannich, Maik Gollasch, Diana A Grohme, Beatriz F Côrte-Real, Roman G Gerlach, Marijana Basic, Athanasios Typas, Chuan Wu, Jens M Titze, Jonathan Jantsch, Michael Boschmann, Ralf Dechend, Markus Kleinewietfeld, Stefan Kempa, Peer Bork, Ralf A Linker, Eric J Alm, Dominik N Müller
A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (TH 17) cells, which can also contribute to hypertension. Induction of TH 17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating TH 17 cells...
November 30, 2017: Nature
#35
REVIEW
Konstantin Licht, Michael F Jantsch
The RNA editing enzyme ADAR1 seemingly has more functions besides RNA editing. Mouse models lacking ADAR1 and sensors of foreign RNA show that RNA editing by ADAR1 plays a crucial role in the innate immune response. Still, RNA editing alone cannot explain all observed phenotypes. Thus, additional roles for ADAR1 must exist. Binding of ADAR1 to RNA is independent of its RNA editing function. Thus, ADAR1 may compete with other RNA-binding proteins. A very recent manuscript elaborates on this and reports competition of ADAR1 with STAUFEN1, thereby modulating RNA-degradation...
November 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
#36
COMPARATIVE STUDY
Roman G Gerlach, Steffi Walter, Michael McClelland, Christiane Schmidt, Matthias Steglich, Rita Prager, Jennifer K Bender, Stephan Fuchs, Christoph Schoerner, Wolfgang Rabsch, Werner Lang, Jonathan Jantsch
Infections of very young children or immunocompromised people with Salmonella of higher subspecies are a well-known phenomenon often associated with contact to cold-blooded animals. We describe the molecular characterization of three S. enterica subsp. diarizonae strains, isolated consecutively over a period of several months from a hospital patient suffering from diarrhea and sepsis with fatal outcome. With the initial isolate the first complete genome sequence of a member of subsp. diarizonae is provided and based on this reference we revealed the genomic differences between the three isolates by use of next-generation sequencing and confirmed by phenotypical tests...
December 2017: International Journal of Medical Microbiology: IJMM
#37
REVIEW
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
#38
EDITORIAL
Andrea Barta, Michael F Jantsch
No abstract text is available yet for this article.
May 4, 2017: RNA Biology
#39
JOURNAL ARTICLE
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
#40
REVIEW
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...
September 2, 2017: RNA Biology
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