Matthias W Hentze

Summary

Affiliation: European Molecular Biology Laboratory
Country: Germany

Publications

  1. ncbi Balancing acts: molecular control of mammalian iron metabolism
    Matthias W Hentze
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Cell 117:285-97. 2004
  2. doi mRNA 3'end processing: A tale of the tail reaches the clinic
    Ina Hollerer
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
    EMBO Mol Med 6:16-26. 2014
  3. pmc Abnormal body iron distribution and erythropoiesis in a novel mouse model with inducible gain of iron regulatory protein (IRP)-1 function
    D Casarrubea
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    J Mol Med (Berl) 91:871-81. 2013
  4. pmc Systems analysis of iron metabolism: the network of iron pools and fluxes
    Tiago J S Lopes
    Max Delbrueck Centrum of Molecular Medicine, Berlin Buch, Germany
    BMC Syst Biol 4:112. 2010
  5. doi Two to tango: regulation of Mammalian iron metabolism
    Matthias W Hentze
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Cell 142:24-38. 2010
  6. doi The REM phase of gene regulation
    Matthias W Hentze
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Trends Biochem Sci 35:423-6. 2010
  7. ncbi Physiologic systemic iron metabolism in mice deficient for duodenal Hfe
    Maja Vujic Spasic
    Molecular Medicine Partnership Unit, University of Heidelberg, Germany
    Blood 109:4511-7. 2007
  8. doi The SXL-UNR corepressor complex uses a PABP-mediated mechanism to inhibit ribosome recruitment to msl-2 mRNA
    Kent E Duncan
    European Molecular Biology Laboratory, Heidelberg, Germany
    Mol Cell 36:571-82. 2009
  9. doi SMAD7 controls iron metabolism as a potent inhibitor of hepcidin expression
    Katarzyna Mleczko-Sanecka
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
    Blood 115:2657-65. 2010
  10. doi Bone morphogenetic protein (BMP)-responsive elements located in the proximal and distal hepcidin promoter are critical for its response to HJV/BMP/SMAD
    Guillem Casanovas
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 153, 69120, Heidelberg, Germany
    J Mol Med (Berl) 87:471-80. 2009

Detail Information

Publications87

  1. ncbi Balancing acts: molecular control of mammalian iron metabolism
    Matthias W Hentze
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Cell 117:285-97. 2004
    ..This has provided novel insights into gene regulation and unveiled remarkable links to the immune system...
  2. doi mRNA 3'end processing: A tale of the tail reaches the clinic
    Ina Hollerer
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
    EMBO Mol Med 6:16-26. 2014
    ..We summarize and discuss the paradigmatic shift in the understanding of 3'end processing as a mechanism of posttranscriptional gene regulation that has reached clinical medicine. ..
  3. pmc Abnormal body iron distribution and erythropoiesis in a novel mouse model with inducible gain of iron regulatory protein (IRP)-1 function
    D Casarrubea
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    J Mol Med (Berl) 91:871-81. 2013
    ..Moreover, it opens novel avenues to study diseases associated with abnormally high IRP1 activity, such as Parkinson's disease or Friedreich's ataxia...
  4. pmc Systems analysis of iron metabolism: the network of iron pools and fluxes
    Tiago J S Lopes
    Max Delbrueck Centrum of Molecular Medicine, Berlin Buch, Germany
    BMC Syst Biol 4:112. 2010
    ..Iron deficiency as well as excess of iron are frequent and serious human disorders. They can affect every cell, but also the organism as a whole...
  5. doi Two to tango: regulation of Mammalian iron metabolism
    Matthias W Hentze
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Cell 142:24-38. 2010
    ..We also highlight some of the current questions in mammalian iron metabolism and discuss therapeutic opportunities arising from a better understanding of the underlying biological principles...
  6. doi The REM phase of gene regulation
    Matthias W Hentze
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Trends Biochem Sci 35:423-6. 2010
    ....
  7. ncbi Physiologic systemic iron metabolism in mice deficient for duodenal Hfe
    Maja Vujic Spasic
    Molecular Medicine Partnership Unit, University of Heidelberg, Germany
    Blood 109:4511-7. 2007
    ....
  8. doi The SXL-UNR corepressor complex uses a PABP-mediated mechanism to inhibit ribosome recruitment to msl-2 mRNA
    Kent E Duncan
    European Molecular Biology Laboratory, Heidelberg, Germany
    Mol Cell 36:571-82. 2009
    ..Our results uncover an important regulatory mechanism of Drosophila dosage compensation and provide insight into PABP-dependent translational control by 3' UTR-bound regulatory proteins...
  9. doi SMAD7 controls iron metabolism as a potent inhibitor of hepcidin expression
    Katarzyna Mleczko-Sanecka
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
    Blood 115:2657-65. 2010
    ..This work identifies a potent inhibitory factor for hepcidin expression and uncovers a negative feedback pathway for hepcidin regulation, providing insight into a mechanism how hepcidin expression may be limited to avoid iron deficiency...
  10. doi Bone morphogenetic protein (BMP)-responsive elements located in the proximal and distal hepcidin promoter are critical for its response to HJV/BMP/SMAD
    Guillem Casanovas
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 153, 69120, Heidelberg, Germany
    J Mol Med (Berl) 87:471-80. 2009
    ..As such, they provide important new information furthering our understanding of disorders of iron metabolism and the anemia of inflammation...
  11. ncbi Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2)
    Bruno Galy
    European Molecular Biology Laboratory, Heidelberg, Germany
    Blood 106:2580-9. 2005
    ..Furthermore, this work uncovers aspects of mammalian iron metabolism that can or cannot be compensated for by the expression of IRP1...
  12. doi Hfe acts in hepatocytes to prevent hemochromatosis
    Maja Vujic Spasic
    Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, 69120 Heidelberg, Germany
    Cell Metab 7:173-8. 2008
    ..This work demonstrates that local Hfe expression in hepatocytes serves to maintain physiological iron homeostasis, answering a long-standing question in medicine and explaining earlier clinical observations...
  13. pmc Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation
    Joachim B Kunz
    Department for Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany
    RNA 12:1015-22. 2006
    ..Stimulation of translation is independent of this interaction and is determined by other regions of the hUpf3 protein, indicating the presence of different downstream pathways of hUpf3 proteins either in NMD or in translation...
  14. pmc Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3' UTR: translational repression for dosage compensation
    Kent Duncan
    Gene Expression Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
    Genes Dev 20:368-79. 2006
    ..Our results reveal a novel functional role for UNR as a translational repressor and indicate that UNR is a key component of a "fail-safe" dosage compensation regulatory system that prevents toxic MSL-2 synthesis in female cells...
  15. doi Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenum
    Bruno Galy
    European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, Germany
    Cell Metab 7:79-85. 2008
    ..IRPs are thus essential for intestinal function and organismal survival and coordinate the synthesis of key iron metabolism proteins in the duodenum...
  16. pmc The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice
    Mirco Castoldi
    Department of Pediatric Hematology, Oncology, and Immunology, University of Heidelberg, Heidelberg, Germany
    J Clin Invest 121:1386-96. 2011
    ..These data help to explain the increased Hamp mRNA levels and subsequent iron deficiency in mice with reduced miR-122 levels and establish a direct mechanistic link between miR-122 and the regulation of systemic iron metabolism...
  17. doi Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by iron regulatory proteins
    Mayka Sanchez
    European Molecular Biology Laboratory EMBL, Heidelberg, Germany
    Blood 118:e168-79. 2011
    ..This work investigates cellular iron metabolism in unprecedented depth and defines a wide network of mRNAs and proteins with iron-dependent regulation, IRP-dependent regulation, or both...
  18. ncbi Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin
    Thomas Herrmann
    Department of Internal Medicine IV, University of Heidelberg, Bergheimer Strasse 58, 69115 Heidelberg, Germany
    J Mol Med (Berl) 82:39-48. 2004
    ..Rather, the duodenal ferric reductase Dcytb may act as a possible mediator of iron overload in Hfe deficiency...
  19. ncbi A dual inhibitory mechanism restricts msl-2 mRNA translation for dosage compensation in Drosophila
    Karsten Beckmann
    Gene Expression Unit, European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 122:529-40. 2005
    ..This failsafe mechanism thus forms the molecular basis of a critical step in dosage compensation. The results also elucidate a two step principle of translational control via multiple regulatory sites within an mRNA...
  20. doi Drosophila miR2 primarily targets the m7GpppN cap structure for translational repression
    Agnieszka Zdanowicz
    European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany
    Mol Cell 35:881-8. 2009
    ....
  21. pmc A co-repressor assembly nucleated by Sex-lethal in the 3'UTR mediates translational control of Drosophila msl-2 mRNA
    Marica Grskovic
    Gene Expression Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    EMBO J 22:5571-81. 2003
    ..Our data support a model where dSXL binding to the 3'UTR of msl-2 mRNA activates the translational repressor domain, thereby enabling it to recruit co-repressors in a specific fashion...
  22. doi In vivo role(s) of the iron regulatory proteins (IRP) 1 and 2 in aseptic local inflammation
    Lydie Viatte
    European Molecular Biology Laboratory EMBL, Meyerhofstrasse 1, 69117, Heidelberg, Germany
    J Mol Med (Berl) 87:913-21. 2009
    ..Our data indicate that the response of Irp1 (-/-) and Irp2 (-/-) mice to acute local inflammation is largely preserved...
  23. pmc Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways
    Pavel V Ivanov
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
    EMBO J 27:736-47. 2008
    ..The EJC, with UPF2 or UPF3b as a cofactor, interferes with physiological termination through UPF1. This model integrates previously competing models of NMD and suggests a mechanistic basis for alternative NMD pathways...
  24. doi Cell-autonomous and systemic context-dependent functions of iron regulatory protein 2 in mammalian iron metabolism
    Dunja Ferring-Appel
    European Molecular Biology Laboratory, Heidelberg, Germany
    Blood 113:679-87. 2009
    ..This work defines the respective roles of IRP2 in the determination of critical body iron parameters such as organ iron loading and erythropoiesis...
  25. pmc Internal ribosome entry sequence-mediated translation initiation triggers nonsense-mediated decay
    Jill A Holbrook
    European Molecular Biology Laboratory, University Hospital Heidelberg, Molecular Medicine Partnership Unit, University of Heidelberg, Im Neuenheimer Feld 150, Heidelberg 69120, Germany
    EMBO Rep 7:722-6. 2006
    ..These data generalize the previous model and suggest that translation per se, irrespective of how it is initiated, can mediate NMD...
  26. doi Translational control via protein-regulated upstream open reading frames
    Jan Medenbach
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Cell 145:902-13. 2011
    ..We propose that protein-regulated uORFs constitute a systematic principle for the regulation of protein synthesis...
  27. doi A bone morphogenetic protein (BMP)-responsive element in the hepcidin promoter controls HFE2-mediated hepatic hepcidin expression and its response to IL-6 in cultured cells
    Maria Vittoria Verga Falzacappa
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany
    J Mol Med (Berl) 86:531-40. 2008
    ..These data uncover a missing link in the HFE2-mediated control of hepcidin expression and suggest that the BMP-RE controls hepcidin promoter activity mediated by HFE2 and inflammatory stimuli...
  28. ncbi Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis
    Martina Muckenthaler
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Nat Genet 34:102-7. 2003
    ..We propose that inappropriate regulatory cues from the liver underlie greater duodenal iron absorption, possibly involving the ferric reductase Cybrd1...
  29. doi p38 MAPK controls prothrombin expression by regulated RNA 3' end processing
    Sven Danckwardt
    Department of Pediatric Oncology, Hematology, and Immunology, University of Heidelberg, Heidelberg, Germany
    Mol Cell 41:298-310. 2011
    ..Regulated 3' end processing thus emerges as a key mechanism of gene regulation with broad biological and medical implications...
  30. doi Iron regulatory proteins secure mitochondrial iron sufficiency and function
    Bruno Galy
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Cell Metab 12:194-201. 2010
    ..These results uncover a major role of the IRPs in cell biology: to ensure adequate iron supply to the mitochondrion for proper function of this critical organelle...
  31. ncbi Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation
    Rolf Thermann
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Nature 447:875-8. 2007
    ..These results directly show the inhibition of m7GpppG cap-mediated translation initiation as the mechanism of miR2 function, and uncover pseudo-polysomal messenger ribonucleoprotein assemblies that may help to explain earlier findings...
  32. pmc Mechanism of translational regulation by miR-2 from sites in the 5' untranslated region or the open reading frame
    Francesca Moretti
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    RNA 16:2493-502. 2010
    ..Using single or dual binding sites, it also reveals a biological rationale for the high prevalence of miR regulatory sites in the 3'UTR...
  33. ncbi Molecular analysis of iron overload in beta2-microglobulin-deficient mice
    Martina U Muckenthaler
    European Molecular Biology Laboratory, D 69117, Heidelberg, Germany
    Blood Cells Mol Dis 33:125-31. 2004
    ....
  34. pmc Translation initiation by the c-myc mRNA internal ribosome entry sequence and the poly(A) tail
    Christian Thoma
    European Molecular Biology Laboratory EMBL, 69117 Heidelberg, Germany
    RNA 14:1579-89. 2008
    ..The mechanistic distinctions from cap-dependent translation may allow specific translational control of the c-myc mRNA and possibly other cellular mRNAs that initiate translation via IRESs...
  35. pmc SIREs: searching for iron-responsive elements
    Monica Campillos
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Nucleic Acids Res 38:W360-7. 2010
    ..The SIREs (Search for iron-responsive elements) web server is freely available on the web at http://ccbg.imppc.org/sires/index.html...
  36. pmc The hierarchy of exon-junction complex assembly by the spliceosome explains key features of mammalian nonsense-mediated mRNA decay
    Niels H Gehring
    Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany
    PLoS Biol 7:e1000120. 2009
    ..Based on this systematic analysis of EJC assembly by the spliceosome, we propose a model of how a functional EJC is assembled in a strictly sequential and hierarchical fashion, including nuclear splicing-dependent and cytoplasmic steps...
  37. ncbi STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation
    Maria Vittoria Verga Falzacappa
    Molecular Medicine Partnership Unit, University of Heidelberg, Heidelberg, Germany
    Blood 109:353-8. 2007
    ..These results identify a missing link in the acute-phase activation of hepcidin and establish STAT3 as a key effector of baseline hepcidin expression and during inflammatory conditions...
  38. ncbi Iron regulation and the cell cycle: identification of an iron-responsive element in the 3'-untranslated region of human cell division cycle 14A mRNA by a refined microarray-based screening strategy
    Mayka Sanchez
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    J Biol Chem 281:22865-74. 2006
    ..This work describes a new experimental strategy to explore the IRE/IRP regulatory network and uncovers a previously unrecognized regulatory link between iron metabolism and the cell cycle...
  39. ncbi Generation of conditional alleles of the murine Iron Regulatory Protein (IRP)-1 and -2 genes
    Bruno Galy
    European Molecular Biology Laboratory, Heidelberg, Germany
    Genesis 43:181-8. 2005
    ..If not removed, the gene trap construct causes partially penetrant embryonic lethality unrelated to IRP deficiency when inserted within the Irp1 but not the Irp2 locus. We discuss the implications for functional genomics in the mouse...
  40. ncbi Bruno acts as a dual repressor of oskar translation, promoting mRNA oligomerization and formation of silencing particles
    Marina Chekulaeva
    Developmental Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Cell 124:521-33. 2006
    ..Bruno-dependent mRNA oligomerization into silencing particles emerges as a mode of translational control that may be particularly suited to coupling with mRNA transport...
  41. doi System-wide identification of RNA-binding proteins by interactome capture
    Alfredo Castello
    European Molecular Biology Laboratory EMBL, Heidelberg, Germany
    Nat Protoc 8:491-500. 2013
    ..Interactome capture can also be broadly used to compare different biological states, including metabolic stress, cell cycle, differentiation, development or the response to drugs...
  42. ncbi miChip: a microarray platform for expression profiling of microRNAs based on locked nucleic acid (LNA) oligonucleotide capture probes
    Mirco Castoldi
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 156, D 69210 Heidelberg, Germany
    Methods 43:146-52. 2007
    ..Moreover, they enable high affinity hybridizations yielding accurate signals that discriminate between single nucleotide differences and hence closely related miRNA family members...
  43. doi The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation
    Flavia D'Alessio
    University of Heidelberg, Department of Pediatric Oncology, Hematology and Immunology, Heidelberg, Germany
    J Hepatol 57:1052-60. 2012
    ..Here, we investigate whether HFE, TfR2, and HJV physically interact on the surface of hepatocytes...
  44. pmc The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway
    Marcelo H Viegas
    Department of Pediatric Oncology, Hematology and Immunology, Children s Hospital, University of Heidelberg, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany
    Nucleic Acids Res 35:4542-51. 2007
    ..We conclude that cellular concentrations of RNPS1 can modify NMD efficiency and propose that cell type specific co-factor availability represents a novel principle that controls NMD...
  45. ncbi A conserved motif in Argonaute-interacting proteins mediates functional interactions through the Argonaute PIWI domain
    Susanne Till
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Nat Struct Mol Biol 14:897-903. 2007
    ..Proteins containing the conserved Ago hook may thus be important regulatory components of effector complexes in RNA interference...
  46. doi Iron regulatory proteins control a mucosal block to intestinal iron absorption
    Bruno Galy
    European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany
    Cell Rep 3:844-57. 2013
    ..IRPs thus secure sufficient iron transport across absorptive enterocytes by restricting the ferritin "mucosal block" and define a basal set point for iron absorption upon which IRP-independent systemic regulatory inputs are overlaid...
  47. ncbi Unbiased RNAi screen for hepcidin regulators links hepcidin suppression to proliferative Ras/RAF and nutrient-dependent mTOR signaling
    Katarzyna Mleczko-Sanecka
    Department of Pediatric Oncology, Hematology and Immunology, and
    Blood 123:1574-85. 2014
    ....
  48. doi PABP and the poly(A) tail augment microRNA repression by facilitated miRISC binding
    Francesca Moretti
    European Molecular Biology Laboratory, Heidelberg, Germany
    Nat Struct Mol Biol 19:603-8. 2012
    ..We integrated these data into a revised model for the function of PABP and the poly(A) tail in miRNA-mediated translational repression...
  49. pmc A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA)
    Mirco Castoldi
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany
    RNA 12:913-20. 2006
    ..The superior detection sensitivity eliminates the need for RNA size selection and/or amplification. MiChip will greatly simplify miRNA expression profiling of biological and clinical samples...
  50. pmc Eukaryotic translation initiation factor 4GI and p97 promote cellular internal ribosome entry sequence-driven translation
    Patrick Hundsdoerfer
    Gene Expression Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Proc Natl Acad Sci U S A 102:13421-6. 2005
    ....
  51. pmc The uORF-containing thrombopoietin mRNA escapes nonsense-mediated decay (NMD)
    Clemens Stockklausner
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, 69120 Heidelberg, Germany
    Nucleic Acids Res 34:2355-63. 2006
    ..Thus, regulation of TPO expression is independent of NMD, implying that mRNAs bearing uORFs cannot generally be considered to represent NMD targets...
  52. pmc Splicing factors stimulate polyadenylation via USEs at non-canonical 3' end formation signals
    Sven Danckwardt
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Germany
    EMBO J 26:2658-69. 2007
    ..These data uncover a novel mechanism that functionally links the splicing and 3' end formation machineries of multiple cellular mRNAs in an USE-dependent manner...
  53. ncbi Enhancement of IRES-mediated translation of the c-myc and BiP mRNAs by the poly(A) tail is independent of intact eIF4G and PABP
    Christian Thoma
    EMBL Heidelberg, Gene Expression Programme, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Mol Cell 15:925-35. 2004
    ..The polyadenylated mRNA translation from cellular IRESs is also profoundly sensitive to eIF4A activity in vitro. These mechanistic and molecular distinctions implicate the potential for a new layer of translational control mechanisms...
  54. pmc Mechanism of escape from nonsense-mediated mRNA decay of human beta-globin transcripts with nonsense mutations in the first exon
    Gabriele Neu-Yilik
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
    RNA 17:843-54. 2011
    ..Furthermore, our data uncover a reason why the position of a nonsense mutation alone does not suffice to predict the fate of the affected mRNA and its effect on protein expression...
  55. pmc The IronChip evaluation package: a package of perl modules for robust analysis of custom microarrays
    Yevhen Vainshtein
    MMPU, Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
    BMC Bioinformatics 11:112. 2010
    ..The use of customized DNA microarrays improves overall data quality in many situations, however, only if for these specifically designed microarrays analysis tools are available...
  56. doi Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network
    Martina U Muckenthaler
    Molecular Medicine Partnership Unit, Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, D 69120 Heidelberg, Germany
    Annu Rev Nutr 28:197-213. 2008
    ..We also discuss how the IRE/IRP regulatory system communicates with the hepcidin/ferroportin system to connect the control networks for systemic and cellular iron balance...
  57. pmc Targeted mutagenesis of the murine IRP1 and IRP2 genes reveals context-dependent RNA processing differences in vivo
    Bruno Galy
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    RNA 10:1019-25. 2004
    ..We discuss the implications for the understanding of RNA processing and for targeting strategies for functional genomics in the mouse...
  58. doi Tethering assays to investigate nonsense-mediated mRNA decay activating proteins
    Niels H Gehring
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
    Methods Enzymol 448:467-82. 2008
    ..In this chapter we explicate the cloning of appropriate reporter plasmids and the setup of a tethering experiment with the necessary control experiments. Advantages of the different systems and tags are discussed...
  59. pmc Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells
    Thomas Schell
    European Molecular Biology Laboratory Heidelberg, Gene Expression Programme, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Biochem J 373:775-83. 2003
    ..Components of the exon-exon junction complex or the translational eukaryotic release factor (eRF) 3 were not identified in complexes associated with Hupf1-2tag. We discuss these findings in the context of current models of NMD...
  60. ncbi Homodirectional changes in transcriptome composition and mRNA translation induced by rapamycin and heat shock
    Thomas Preiss
    EMBL Heidelberg, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Nat Struct Biol 10:1039-47. 2003
    ..Thus, signal-induced changes in the transcriptome are amplified at the translational level. These results unveil a higher level of coordinated gene regulation that we refer to as 'potentiation.'..
  61. pmc Pathologies at the nexus of blood coagulation and inflammation: thrombin in hemostasis, cancer, and beyond
    Sven Danckwardt
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
    J Mol Med (Berl) 91:1257-71. 2013
    ..In this review, we will address thrombin's broad roles in diverse (patho)physiological processes in an integrative way. We will also discuss thrombin as an emerging major target for novel therapies. ..
  62. ncbi Nonsense-mediated decay approaches the clinic
    Jill A Holbrook
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, D 69120 Heidelberg, Germany
    Nat Genet 36:801-8. 2004
    ..Potential 'NMD therapeutics' will therefore need to strike a balance between the general physiological benefits of NMD and its detrimental effects in cases of specific genetic mutations...
  63. pmc Nonsense-mediated mRNA decay: from vacuum cleaner to Swiss army knife
    Gabriele Neu-Yilik
    Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany
    Genome Biol 5:218. 2004
    ..Two new approaches have identified physiological NMD substrates, and suggest that NMD functions as a multipurpose tool in the modulation of gene expression...
  64. doi RNA-binding proteins in Mendelian disease
    Alfredo Castello
    European Molecular Biology Laboratory EMBL, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Trends Genet 29:318-27. 2013
    ..We also expect that mRNA interactome capture approaches will aid further exploration of RNA systems biology in varied physiological and pathophysiological settings...
  65. pmc The interaction of the cap-binding complex (CBC) with eIF4G is dispensable for translation in yeast
    Julie Baron-Benhamou
    Gene Expression Programme, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
    RNA 9:654-62. 2003
    ....
  66. ncbi Drosophila sex-lethal inhibits the stable association of the 40S ribosomal subunit with msl-2 mRNA
    Fátima Gebauer
    European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Mol Cell 11:1397-404. 2003
    ..These results elucidate a critical regulatory step for dosage compensation in Drosophila melanogaster...
  67. doi Insights into RNA biology from an atlas of mammalian mRNA-binding proteins
    Alfredo Castello
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 149:1393-406. 2012
    ..Interactome capture is broadly applicable to study mRNA interactome composition and dynamics in varied biological settings...
  68. ncbi Relationships and distinctions in iron-regulatory networks responding to interrelated signals
    Martina Muckenthaler
    European Molecular Biology Laboratory, Heidelberg, Germany
    Blood 101:3690-8. 2003
    ..These findings also demonstrate the broad utility of gene-expression profiling with the IronChip to study iron metabolism and related human diseases...
  69. doi An efficient factor-depleted mammalian in vitro translation system
    Aurelie M Rakotondrafara
    European Molecular Biology Laboratory, Heidelberg, Germany
    Nat Protoc 6:563-71. 2011
    ..The complete procedure can normally be conducted within 1 week and carried out in parallel for multiple (candidate) factors...
  70. pmc Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function
    Nadia Hubert
    European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Proc Natl Acad Sci U S A 99:12345-50. 2002
    ..These results uncover an unexpected complexity of DMT1 expression and regulation, with implications for understanding the physiology, cell biology, and pathophysiology of mammalian iron metabolism...
  71. ncbi Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress
    Khristy Thompson
    Department of Neuroscience and Anatomy, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
    J Neurosci Res 71:46-63. 2003
    ..These results suggest that this mouse may be a model to determine the role of iron mismanagement in neurodegenerative disorders and for testing antioxidant therapeutic strategies...
  72. ncbi Iron-regulatory proteins limit hypoxia-inducible factor-2alpha expression in iron deficiency
    Mayka Sanchez
    Molecular Medicine Partnership Unit, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany
    Nat Struct Mol Biol 14:420-6. 2007
    ..They also show that an IRE that is structurally distinct from, for example, the ferritin mRNA IRE and that has been missed by in silico approaches, can mediate mechanistically similar responses...
  73. ncbi Expression of the subgenomic hepatitis C virus replicon alters iron homeostasis in Huh7 cells
    Carine Fillebeen
    Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, 3755 Cote Ste Catherine Road, Montreal, Que, Canada H3T 1E2
    J Hepatol 47:12-22. 2007
    ..To seek for molecular links, we employed an established cell culture model for viral replication, and assessed how the expression of an HCV subgenomic replicon affects iron metabolism in host Huh7 hepatoma cells...
  74. ncbi Expression of epithelial cell iron-related genes upon infection by Neisseria meningitidis
    Robert A Bonnah
    Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Portland, OR, USA
    Cell Microbiol 6:473-84. 2004
    ..This finding suggests that low IRP activity may be responsible in part for the decrease in TfR-1 mRNA levels. A discussion of these novel findings in relation to MC infection and virulence is provided...
  75. ncbi Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1
    Susanne Ludwiczek
    Department of General Internal Medicine, Clinical Immunology and Infectious Diseases, Innsbruck Medical University, Anichstr 35, A 6020 Innsbruck, Austria
    Nat Med 13:448-54. 2007
    ..Modulation of DMT-1 function by L-type calcium channel blockers emerges as a new pharmacological therapy for the treatment of iron overload disorders...
  76. ncbi A chemiluminescence-based reporter system to monitor nonsense-mediated mRNA decay
    Stephanie Boelz
    Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Im Neuenheimer Feld 156, 69120 Heidelberg, Germany
    Biochem Biophys Res Commun 349:186-91. 2006
    ..Wortmannin treatment enhanced NMD reporter expression in our system in a dose-dependent way, illustrating its utility for small molecule screening...
  77. ncbi IRP1-independent alterations of cardiac iron metabolism in doxorubicin-treated mice
    Gianfranca Corna
    Institute of General Pathology, University of Milan, Via Mangiagalli 31, Milan 20133, Italy
    J Mol Med (Berl) 84:551-60. 2006
    ..The observed IRP2 downmodulation could serve as a means to counteract DOX cardiotoxicity by reducing the "free" cellular iron pool...
  78. ncbi Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements
    Niels H Gehring
    Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg 69120, Germany
    Mol Cell 20:65-75. 2005
    ..These results are integrated into a nonlinear model for mammalian NMD involving alternative routes of entry that converge at a common requirement of UPF1...
  79. pmc Is congenital secondary erythrocytosis/polycythemia caused by activating mutations within the HIF-2 alpha iron-responsive element?
    Melanie J Percy
    Blood 110:2776-7. 2007
  80. ncbi Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse
    Bruno Galy
    Nat Genet 38:967-9; discussion 969-70. 2006
  81. ncbi The molecular circuitry regulating the switch between iron deficiency and overload in mice
    Henry Mok
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 281:7946-51. 2006
    ..We conclude that regulatory alleles, such as Pcm, with highly dynamic changes in iron balance are ideally suited to interrogate the genetic circuitry regulating iron metabolism...
  82. ncbi Abnormally spliced beta-globin mRNAs: a single point mutation generates transcripts sensitive and insensitive to nonsense-mediated mRNA decay
    Sven Danckwardt
    Department of General Pediatrics, Charite, Humboldt University, Berlin, Germany
    Blood 99:1811-6. 2002
    ..It can therefore serve as a useful tool for defining the mechanisms that permit specific transcripts to circumvent the NMD pathway...
  83. pmc Complex translational regulation of BACE1 involves upstream AUGs and stimulatory elements within the 5' untranslated region
    Marija Mihailovich
    San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy
    Nucleic Acids Res 35:2975-85. 2007
    ..Furthermore, we have evidence that a sequence within the region 222-323 of the BACE1 5' UTR has a stimulatory effect on translation that might depend on the presence of trans-acting factors...
  84. ncbi Iron inactivates the RNA polymerase NS5B and suppresses subgenomic replication of hepatitis C Virus
    Carine Fillebeen
    Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, 3755 Cote Sainte Catherine Road, Montreal, Quebec H3T 1E2, Canada
    J Biol Chem 280:9049-57. 2005
    ..Our data provide a direct molecular link between iron and HCV replication...
  85. ncbi Molecular mechanisms of translational control
    Fátima Gebauer
    Centre de Regulacio Genomica, Passeig Maritim 37 49, 08003 Barcelona, Spain
    Nat Rev Mol Cell Biol 5:827-35. 2004
    ..Instead of providing a comprehensive account of the examples that are known at present, we discuss instructive cases that serve as paradigms for different modes of translational control...
  86. ncbi An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice
    Cindy N Roy
    Children s Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 36:481-5. 2004
    ..These data suggest a previously unidentified role for Hfe in innate immunity and ACD...
  87. pmc Iron-mediated degradation of IRP2, an unexpected pathway involving a 2-oxoglutarate-dependent oxygenase activity
    Jian Wang
    Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada
    Mol Cell Biol 24:954-65. 2004
    ..Our results challenge the current model for IRP2 regulation and provide direct pharmacological evidence for the involvement of 2-oxoglutarate-dependent oxygenases in a pathway for IRP2 degradation...