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Author

Jörg Vogel

Bio: Jörg Vogel is an academic researcher from University of Würzburg. The author has contributed to research in topics: RNA & Gene. The author has an hindex of 89, co-authored 216 publications receiving 26988 citations. Previous affiliations of Jörg Vogel include Humboldt State University & Uppsala University.
Topics: RNA, Gene, Small RNA, Non-coding RNA, Transcriptome


Papers
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Journal ArticleDOI
31 Mar 2011-Nature
TL;DR: In this article, tracrRNA, a trans-encoded small RNA with 24-nucleotide complementarity to the repeat regions of crRNA precursor transcripts, is shown to direct the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein.
Abstract: CRISPR/Cas systems constitute a widespread class of immunity systems that protect bacteria and archaea against phages and plasmids, and commonly use repeat/spacer-derived short crRNAs to silence foreign nucleic acids in a sequence-specific manner. Although the maturation of crRNAs represents a key event in CRISPR activation, the responsible endoribonucleases (CasE, Cas6, Csy4) are missing in many CRISPR/Cas subtypes. Here, differential RNA sequencing of the human pathogen Streptococcus pyogenes uncovered tracrRNA, a trans-encoded small RNA with 24-nucleotide complementarity to the repeat regions of crRNA precursor transcripts. We show that tracrRNA directs the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein; all these components are essential to protect S. pyogenes against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders.

2,336 citations

Journal ArticleDOI
11 Mar 2010-Nature
TL;DR: A novel differential approach selective for the 5′ end of primary transcripts is presented, establishing a paradigm for mapping and annotating the primary transcriptomes of many living species and discovering hundreds of transcriptional start sites within operons, and opposite to annotated genes.
Abstract: Genome sequencing of Helicobacter pylori has revealed the potential proteins and genetic diversity of this prevalent human pathogen, yet little is known about its transcriptional organization and noncoding RNA output. Massively parallel cDNA sequencing (RNA-seq) has been revolutionizing global transcriptomic analysis. Here, using a novel differential approach (dRNA-seq) selective for the 5' end of primary transcripts, we present a genome-wide map of H. pylori transcriptional start sites and operons. We discovered hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. We also discovered an unexpected number of approximately 60 small RNAs including the epsilon-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs. Our approach establishes a paradigm for mapping and annotating the primary transcriptomes of many living species.

1,094 citations

Journal ArticleDOI
TL;DR: Recent studies have served to clarify the abundance of remaining questions about how, when, and why sRNA-mediated regulation is of such importance to bacterial lifestyles.

1,057 citations

Journal ArticleDOI
Jonas Schulte-Schrepping1, Nico Reusch1, Daniela Paclik2, Kevin Baßler1, Stephan Schlickeiser2, Bowen Zhang3, Benjamin Krämer4, Tobias Krammer, Sophia Brumhard2, Lorenzo Bonaguro1, Elena De Domenico5, Daniel Wendisch2, Martin Grasshoff3, Theodore S. Kapellos1, Michael Beckstette3, Tal Pecht1, Adem Saglam5, Oliver Dietrich, Henrik E. Mei6, Axel Schulz6, Claudia Conrad2, Désirée Kunkel2, Ehsan Vafadarnejad, Cheng-Jian Xu7, Cheng-Jian Xu3, Arik Horne1, Miriam Herbert1, Anna Drews5, Charlotte Thibeault2, Moritz Pfeiffer2, Stefan Hippenstiel2, Andreas C. Hocke2, Holger Müller-Redetzky2, Katrin-Moira Heim2, Felix Machleidt2, Alexander Uhrig2, Laure Bosquillon de Jarcy2, Linda Jürgens2, Miriam Stegemann2, Christoph R. Glösenkamp2, Hans-Dieter Volk2, Christine Goffinet2, Markus Landthaler8, Emanuel Wyler8, Philipp Georg2, Maria Schneider2, Chantip Dang-Heine2, Nick Neuwinger2, Kai Kappert2, Rudolf Tauber2, Victor M. Corman2, Jan Raabe4, Kim Melanie Kaiser4, Michael To Vinh4, Gereon Rieke4, Christian Meisel2, Thomas Ulas5, Matthias Becker5, Robert Geffers, Martin Witzenrath2, Christian Drosten2, Norbert Suttorp2, Christof von Kalle2, Florian Kurth9, Florian Kurth2, Florian Kurth10, Kristian Händler5, Joachim L. Schultze5, Joachim L. Schultze1, Anna C. Aschenbrenner7, Anna C. Aschenbrenner1, Yang Li3, Yang Li7, Jacob Nattermann4, Birgit Sawitzki2, Antoine-Emmanuel Saliba, Leif E. Sander2, Angel Angelov, Robert Bals, Alexander Bartholomäus, Anke Becker, Daniela Bezdan, Ezio Bonifacio, Peer Bork, Thomas Clavel, Maria Colomé-Tatché, Andreas Diefenbach, Alexander T. Dilthey, Nicole Fischer, Konrad U. Förstner, Julia-Stefanie Frick, Julien Gagneur, Alexander Goesmann, Torsten Hain, Michael Hummel, Stefan Janssen, Jörn Kalinowski, René Kallies, Birte Kehr, Andreas Keller, Sarah Kim-Hellmuth, Christoph Klein, Oliver Kohlbacher, Jan O. Korbel, Ingo Kurth, Kerstin U. Ludwig, Oliwia Makarewicz, Manja Marz, Alice C. McHardy, Christian Mertes, Markus M. Nöthen, Peter Nürnberg, Uwe Ohler, Stephan Ossowski, Jörg Overmann, Silke Peter, Klaus Pfeffer, Anna R. Poetsch, Alfred Pühler, Nikolaus Rajewsky, Markus Ralser, Olaf Rieß, Stephan Ripke, Ulisses Nunes da Rocha, Philip Rosenstiel, Philipp H. Schiffer, Eva-Christina Schulte, Alexander Sczyrba, Oliver Stegle, Jens Stoye, Fabian J. Theis, Janne Vehreschild, Jörg Vogel, Max von Kleist, Andreas Walker, Jörn Walter, Dagmar Wieczorek, John Ziebuhr 
17 Sep 2020-Cell
TL;DR: This study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

1,042 citations

Journal ArticleDOI
TL;DR: The salient structural and functional features of Hfq are described and possible mechanisms by which this protein can promote RNA interactions to catalyse specific and rapid regulatory responses in vivo are discussed.
Abstract: Hfq is an RNA-binding protein that is common to diverse bacterial lineages and has key roles in the control of gene expression. By facilitating the pairing of small RNAs with their target mRNAs, Hfq affects the translation and turnover rates of specific transcripts and contributes to complex post-transcriptional networks. These functions of Hfq can be attributed to its ring-like oligomeric architecture, which presents two non-equivalent binding surfaces that are capable of multiple interactions with RNA molecules. Distant homologues of Hfq occur in archaea and eukaryotes, reflecting an ancient origin for the protein family and hinting at shared functions. In this Review, we describe the salient structural and functional features of Hfq and discuss possible mechanisms by which this protein can promote RNA interactions to catalyse specific and rapid regulatory responses in vivo.

899 citations


Cited by
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Journal ArticleDOI
17 Aug 2012-Science
TL;DR: This study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.
Abstract: Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.

12,865 citations

Journal ArticleDOI
15 Feb 2013-Science
TL;DR: The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage as discussed by the authors.
Abstract: Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.

12,265 citations

01 Feb 2013
TL;DR: Two different type II CRISPR/Cas systems are engineered and it is demonstrated that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.
Abstract: Genome Editing Clustered regularly interspaced short palindromic repeats (CRISPR) function as part of an adaptive immune system in a range of prokaryotes: Invading phage and plasmid DNA is targeted for cleavage by complementary CRISPR RNAs (crRNAs) bound to a CRISPR-associated endonuclease (see the Perspective by van der Oost). Cong et al. (p. 819, published online 3 January) and Mali et al. (p. 823, published online 3 January) adapted this defense system to function as a genome editing tool in eukaryotic cells. A bacterial genome defense system is adapted to function as a genome-editing tool in mammalian cells. [Also see Perspective by van der Oost] Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.

10,746 citations

Journal ArticleDOI
TL;DR: A set of tools for Cas9-mediated genome editing via nonhomologous end joining (NHEJ) or homology-directed repair (HDR) in mammalian cells, as well as generation of modified cell lines for downstream functional studies are described.
Abstract: Targeted nucleases are powerful tools for mediating genome alteration with high precision. The RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system can be used to facilitate efficient genome engineering in eukaryotic cells by simply specifying a 20-nt targeting sequence within its guide RNA. Here we describe a set of tools for Cas9-mediated genome editing via nonhomologous end joining (NHEJ) or homology-directed repair (HDR) in mammalian cells, as well as generation of modified cell lines for downstream functional studies. To minimize off-target cleavage, we further describe a double-nicking strategy using the Cas9 nickase mutant with paired guide RNAs. This protocol provides experimentally derived guidelines for the selection of target sites, evaluation of cleavage efficiency and analysis of off-target activity. Beginning with target design, gene modifications can be achieved within as little as 1-2 weeks, and modified clonal cell lines can be derived within 2-3 weeks.

8,663 citations

Journal ArticleDOI
15 Feb 2013-Science
TL;DR: The type II bacterial CRISPR system is engineer to function with custom guide RNA (gRNA) in human cells to establish an RNA-guided editing tool for facile, robust, and multiplexable human genome engineering.
Abstract: Bacteria and archaea have evolved adaptive immune defenses, termed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems, that use short RNA to direct degradation of foreign nucleic acids. Here, we engineer the type II bacterial CRISPR system to function with custom guide RNA (gRNA) in human cells. For the endogenous AAVS1 locus, we obtained targeting rates of 10 to 25% in 293T cells, 13 to 8% in K562 cells, and 2 to 4% in induced pluripotent stem cells. We show that this process relies on CRISPR components; is sequence-specific; and, upon simultaneous introduction of multiple gRNAs, can effect multiplex editing of target loci. We also compute a genome-wide resource of ~190 K unique gRNAs targeting ~40.5% of human exons. Our results establish an RNA-guided editing tool for facile, robust, and multiplexable human genome engineering.

8,197 citations