Prof. Dr. Markus Landthaler
Profil
Forschungsthemen1
Von der Zelle zu Prozessen: Fortschritte und Herausforderungen in der Einzelbiologie
Quelle ↗Förderer: DFG sonstige Programme Zeitraum: 06/2018 - 06/2018 Projektleitung: Prof. Dr. Markus Landthaler
Mögliche Industrie-Partner10
Stand: 26.4.2026, 19:48:44 (Top-K=20, Min-Cosine=0.4)
- 12 Treffer64.6%
- Translation for Massive Open Online CoursesP64.6%
- Translation for Massive Open Online Courses
- 11 Treffer64.6%
- Translation for Massive Open Online CoursesP64.6%
- Translation for Massive Open Online Courses
- 11 Treffer64.6%
- Translation for Massive Open Online CoursesP64.6%
- Translation for Massive Open Online Courses
Higher Functions - Sistemas Informáticos Inteligentes
P21 Treffer60.0%- QTLeap - Qualitätsübersetzung durch tiefe SprachanalysemethodenP60.0%
- QTLeap - Qualitätsübersetzung durch tiefe Sprachanalysemethoden
- 89 Treffer59.2%
- Engineering of New-Generation Protein Secretion SystemsP59.2%
- Engineering of New-Generation Protein Secretion Systems
- 89 Treffer59.2%
- Engineering of New-Generation Protein Secretion SystemsP59.2%
- Engineering of New-Generation Protein Secretion Systems
- 89 Treffer59.2%
- Engineering of New-Generation Protein Secretion SystemsP59.2%
- Engineering of New-Generation Protein Secretion Systems
- 56 Treffer57.6%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other StrategiesP57.6%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other Strategies
- 57 Treffer57.6%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other StrategiesP57.6%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other Strategies
- 57 Treffer57.6%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other StrategiesP57.6%
- Validating C. Elegans Healthspan Model for Better Understanding Factors Causing Health and Disease, to Develop Evidence Based Prevention, Diagnostic, Therapeutic and Other Strategies
Publikationen25
Top 25 nach Zitationen — Quelle: OpenAlex (BAAI/bge-m3 embedded für Matching).
Nature · 8431 Zitationen · DOI
Cell · 3660 Zitationen · DOI
Cell · 2931 Zitationen · DOI
Molecular Cell · 1938 Zitationen · DOI
Molecular Cell · 1850 Zitationen · DOI
Cell · 1592 Zitationen · DOI
Molecular Cell · 1273 Zitationen · DOI
Cell Reports · 1211 Zitationen · DOI
Circular RNAs (circRNAs) are a large class of animal RNAs. To investigate possible circRNA functions, it is important to understand circRNA biogenesis. Besides human ALU repeats, sequence features that promote exon circularization are largely unknown. We experimentally identified circRNAs in C. elegans. Reverse complementary sequences between introns bracketing circRNAs were significantly enriched in comparison to linear controls. By scoring the presence of reverse complementary sequences in human introns, we predicted and experimentally validated circRNAs. We show that introns bracketing circRNAs are highly enriched in RNA editing or hyperediting events. Knockdown of the double-strand RNA-editing enzyme ADAR1 significantly and specifically upregulated circRNA expression. Together, our data support a model of animal circRNA biogenesis in which competing RNA-RNA interactions of introns form larger structures that promote circularization of embedded exons, whereas ADAR1 antagonizes circRNA expression by melting stems within these interactions.
Current Biology · 841 Zitationen · DOI
Science · 830 Zitationen · DOI
CD4+ T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acidification, EBNA1, the dominant CD4+ T cell antigen of latent Epstein-Barr virus infection, slowly accumulated in cytosolic autophagosomes. In addition, inhibition of autophagy decreased recognition by EBNA1-specific CD4+ T cell clones. Thus, lysosomal processing after autophagy may contribute to MHC class II-restricted surveillance of long-lived endogenous antigens including nuclear proteins relevant to disease.
Molecular Cell · 743 Zitationen · DOI
Cell · 665 Zitationen · DOI
RNA · 617 Zitationen · DOI
A large number of miRNAs have recently been discovered in plants and animals. Development of reverse genetic approaches that act to inhibit microRNA function would facilitate the study of this new class of noncoding RNA. Here we show that 2'-O-methyl oligoribonucleotides, but not 2'-deoxyoligonucleotides specifically inactivate the RNAi activity associated with miRNA-protein complexes in human cell extracts as well as in cultured human cells.
Current Biology · 553 Zitationen · DOI
Cell · 536 Zitationen · DOI
Proceedings of the National Academy of Sciences · 526 Zitationen · DOI
Recently identified hepatitis C virus (HCV) isolates that are infectious in cell culture provide a genetic system to evaluate the significance of virus-host interactions for HCV replication. We have completed a systematic RNAi screen wherein siRNAs were designed that target 62 host genes encoding proteins that physically interact with HCV RNA or proteins or belong to cellular pathways thought to modulate HCV infection. This includes 10 host proteins that we identify in this study to bind HCV NS5A. siRNAs that target 26 of these host genes alter infectious HCV production >3-fold. Included in this set of 26 were siRNAs that target Dicer, a principal component of the RNAi silencing pathway. Contrary to the hypothesis that RNAi is an antiviral pathway in mammals, as has been reported for subgenomic HCV replicons, siRNAs that target Dicer inhibited HCV replication. Furthermore, siRNAs that target several other components of the RNAi pathway also inhibit HCV replication. MicroRNA profiling of human liver, human hepatoma Huh-7.5 cells, and Huh-7.5 cells that harbor replicating HCV demonstrated that miR-122 is the predominant microRNA in each environment. miR-122 has been previously implicated in positively regulating the replication of HCV genotype 1 replicons. We find that 2'-O-methyl antisense oligonucleotide depletion of miR-122 also inhibits HCV genotype 2a replication and infectious virus production. Our data define 26 host genes that modulate HCV infection and indicate that the requirement for functional RNAi for HCV replication is dominant over any antiviral activity this pathway may exert against HCV.
Nature Methods · 452 Zitationen · DOI
Cell · 382 Zitationen · DOI
RNA · 363 Zitationen · DOI
microRNAs (miRNAs) regulate the expression of mRNAs in animals and plants through miRNA-containing ribonucleoprotein particles (RNPs). At the core of these miRNA silencing effector complexes are the Argonaute (AGO) proteins that bind miRNAs and mediate target mRNA recognition. We generated HEK293 cell lines stably expressing epitope-tagged human AGO proteins and other RNA silencing-related proteins and used these cells to purify miRNA-containing RNPs. Mass spectrometric analyses of the proteins associated with different AGO proteins revealed a common set of helicases and mRNA-binding proteins, among them the three trinucleotide repeat containing proteins 6 (TNRC6A,-B,-C). mRNA microarray analyses of these miRNA-associated RNPs revealed that AGO and TNRC6 proteins bind highly similar sets of transcripts enriched in binding sites for highly expressed endogenous miRNAs, indicating that the TNRC6 proteins are a component of the mRNA-targeting miRNA silencing complex. Together with the very similar proteomic composition of each AGO complex, this result suggests substantial functional redundancy within families of human AGO and TNRC6 proteins. Our results further demonstrate that we have developed an effective biochemical approach to identify physiologically relevant human miRNA targets.
Nature · 343 Zitationen · DOI
iScience · 293 Zitationen · DOI
Detailed knowledge of the molecular biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial for understanding of viral replication, host responses, and disease progression. Here, we report gene expression profiles of three SARS-CoV- and SARS-CoV-2-infected human cell lines. SARS-CoV-2 elicited an approximately two-fold higher stimulation of the innate immune response compared to SARS-CoV in the human epithelial cell line Calu-3, including induction of miRNA-155. Single-cell RNA sequencing of infected cells showed that genes induced by virus infections were broadly upregulated, whereas interferon beta/lambda genes, a pro-inflammatory cytokines such as IL-6, were expressed only in small subsets of infected cells. Temporal analysis suggested that transcriptional activities of interferon regulatory factors precede those of nuclear factor κB. Lastly, we identified heat shock protein 90 (HSP90) as a protein relevant for the infection. Inhibition of the HSP90 activity resulted in a reduction of viral replication and pro-inflammatory cytokine expression in primary human airway epithelial cells.
SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals
2021Nature Communications · 287 Zitationen · DOI
Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy inhibitors (AKT1, SKP2) and reduction of proteins responsible for autophagy initiation (AMPK, TSC2, ULK1), membrane nucleation, and phagophore formation (BECN1, VPS34, ATG14), as well as autophagosome-lysosome fusion (BECN1, ATG14 oligomers). Consequently, phagophore-incorporated autophagy markers LC3B-II and P62 accumulate, which we confirm in a hamster model and lung samples of COVID-19 patients. Single-nucleus and single-cell sequencing of patient-derived lung and mucosal samples show differential transcriptional regulation of autophagy and immune genes depending on cell type, disease duration, and SARS-CoV-2 replication levels. Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC<sub>50</sub> values of 136.7, 7.67, 0.11, and 0.13 μM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19.
Nature Cell Biology · 267 Zitationen · DOI
Journal of Visualized Experiments · 264 Zitationen · DOI
RNA transcripts are subjected to post-transcriptional gene regulation by interacting with hundreds of RNA-binding proteins (RBPs) and microRNA-containing ribonucleoprotein complexes (miRNPs) that are often expressed in a cell-type dependently. To understand how the interplay of these RNA-binding factors affects the regulation of individual transcripts, high resolution maps of in vivo protein-RNA interactions are necessary. A combination of genetic, biochemical and computational approaches are typically applied to identify RNA-RBP or RNA-RNP interactions. Microarray profiling of RNAs associated with immunopurified RBPs (RIP-Chip) defines targets at a transcriptome level, but its application is limited to the characterization of kinetically stable interactions and only in rare cases allows to identify the RBP recognition element (RRE) within the long target RNA. More direct RBP target site information is obtained by combining in vivo UV crosslinking with immunoprecipitation followed by the isolation of crosslinked RNA segments and cDNA sequencing (CLIP). CLIP was used to identify targets of a number of RBPs. However, CLIP is limited by the low efficiency of UV 254 nm RNA-protein crosslinking, and the location of the crosslink is not readily identifiable within the sequenced crosslinked fragments, making it difficult to separate UV-crosslinked target RNA segments from background non-crosslinked RNA fragments also present in the sample. We developed a powerful cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs that we term PAR-CliP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) (see Fig. 1A for an outline of the method). The method relies on the incorporation of photoreactive ribonucleoside analogs, such as 4-thiouridine (4-SU) and 6-thioguanosine (6-SG) into nascent RNA transcripts by living cells. Irradiation of the cells by UV light of 365 nm induces efficient crosslinking of photoreactive nucleoside-labeled cellular RNAs to interacting RBPs. Immunoprecipitation of the RBP of interest is followed by isolation of the crosslinked and coimmunoprecipitated RNA. The isolated RNA is converted into a cDNA library and deep sequenced using Solexa technology. One characteristic feature of cDNA libraries prepared by PAR-CliP is that the precise position of crosslinking can be identified by mutations residing in the sequenced cDNA. When using 4-SU, crosslinked sequences thymidine to cytidine transition, whereas using 6-SG results in guanosine to adenosine mutations. The presence of the mutations in crosslinked sequences makes it possible to separate them from the background of sequences derived from abundant cellular RNAs. Application of the method to a number of diverse RNA binding proteins was reported in Hafner et al.
Proceedings of the National Academy of Sciences · 237 Zitationen · DOI
MicroRNAs play important roles in animal development. Numerous conditional knockout (cKO) studies of Dicer have been performed to interrogate the functions of microRNA during mammalian development. However, because Dicer was recently implicated in the biogenesis of endogenous siRNAs in mammals, it raises the question whether the Dicer cKO defects can be attributable to the loss of microRNAs. Previously, we and others conditionally targeted Dicer and identified its critical roles in embryonic skin morphogenesis. Here, we focus explicitly on microRNAs by taking a parallel strategy with Dgcr8, encoding an essential component of the microprocessor complex that is exclusively required for microRNA biogenesis. With this comparative analysis, we show definitively that the Dicer- and Dgcr8-null skin defects are both striking and indistinguishable. By deep sequencing analysis of microRNA depletion in both Dicer- and Dgcr8-null skin, we demonstrate that most abundantly expressed skin microRNAs are dependent on both Dicer and DGCR8. Our results underscore a specific importance of microRNAs in controlling mammalian skin development.
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Stammdaten
Identität, Organisation und Kontakt aus HU-FIS.
- Name
- Prof. Dr. Markus Landthaler
- Titel
- Prof. Dr.
- Fakultät
- Lebenswissenschaftliche Fakultät
- Institut
- Institut für Biologie
- Arbeitsgruppe
- RNA Biologie (S)
- Telefon
- +49 30 9406-3026
- HU-FIS-Profil
- Quelle ↗
- Zuletzt gescrapt
- 26.4.2026, 01:08:18