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    Chair of Cell and Developmental Biology (Zoology I)

    KRAMER LAB

    The major aim of our research is to understand how spatial aspects of mRNA metabolism contribute to the posttranscriptional regulation of gene expression in eukaryotes.

    Research synopsis

    About half of eukaryotic gene expression regulation is estimated to occur posttranscriptional, with the regulation of mRNA metabolism playing a major role. Thereby, the localisation of an mRNA often determines its function and can be very dynamic. Various triggers for example cause most mRNAs to move from translating polysomes into stress granules, which are macroscopic aggregates of protein and RNA. Bulk mRNAs are believed to be stored in these granules to allow for the selected translation of stress response proteins and can return back to translation after stress release. Another example is the localisation of a specific mRNA to an intracellular sub-compartment, for example for localised translation. The mechanisms that determine and regulate intracellular mRNA localisation still remain poorly understood, in any organism.

    As a model system, we are am using Trypanosoma brucei, a single cell flagellate that shuttles between the tsetse fly insect vector and its mammalian host and is responsible for human African trypanosomiasis. For the questions I am interested in, trypanosomes have several advantages: i) The parasites are true experts in posttranscriptional gene regulation, as they lack any transcriptional control of genes transcribed by RNA polymerase II ii) Trypanosomes frequently change the expression of a large fraction of their genome, during their complex life cycle or in response to stress; many of these changes can be simulated in vitro and are highly useful experimental tools. iii) Trypanosomes have highly asymmetrical cell architectures with well-positioned single organelles, which hugely facilitates the detection and description of positional changes of mRNA molecules or ribonucleoprotein granules (RNA granules).

    Recent publications

    Goos C, Dejung M, Wehman AM, Meyer-Natus E, Schmidt J, SunterJ , Engstler M, Butter F and Kramer S. (2019) Trypanosomes can initiate nuclear export co-transcriptionally. Nucleic Acid research, in press PMID:30418648

    Kramer S and McLennan AG. (2018) The complex enzymology of mRNA decapping: enzymes of four classes cleave pyrophosphate bounds.WIREs RNA 38, e1511–17. PMID:30345629

    Zoltner, M., Krienitz, N., Field, M. C. & Kramer, S (2018). Comparative proteomics of the two T. brucei PABPs suggests that PABP2 controls bulk mRNA. PLoS Necl Trop Dis 12, e0006679. PMID:30040867

    Bannerman, B P, Kramer, S, Dorrell, R . & Carrington, M (2018) Multispecies reconstructions uncover widespread conservation, and lineage-specific elaborations in eukaryotic mRNA metabolism. PLoS ONE 13, e0192633–23. PMID:29561870

    Kramer S (2017). The ApaH-like phosphatase TbALPH1 is the major mRNA decapping enzyme of trypanosomes. PLoS Pathog 13: e1006456 PMID:28628654

    Zimmermann, H., Subota, I., Batram, C., Kramer, S., Janzen, C. J., Jones, N. G., & Engstler, M (2017). A quorum sensing-independent path to stumpy development in Trypanosoma brucei. PLoS Pathog., 13:e1006324–33. PMID:28394929

    Kramer S (2017). Simultaneous detection of mRNA transcription and decay intermediates by dual colour single mRNA FISH on subcellular resolution. Nucleic Acids Res 45: e49 PMID:27940558

    Goos C, Dejung M, Janzen CJ, Butter F and Kramer S (2017). The nuclear proteome of Trypanosoma brucei. PLoS One 12(7):e0181884. PMID:28727848

    full list of publications

    RESEARCH TOPICS

    mRNA granules

    Many non-polysomal mRNAs aggregate into RNA granules, large ribonucleoprotein particles. What is the composition and function of RNA granules and how are they regulated?

    mRNA decay

    The first step in mRNA decay is the removal of the 5' cap. In trypanosomes, this is done by a highly unusual enzyme, an ApaH like phosphatase.

    mRNA export

    We recently found that trypanosomes can export their mRNAs co-transcriptionally.

    CURRENT LAB MEMBERS

    Claudia Moreira

    Nicole Banholzer

    Anna Sophie Kreis

    PhD, Postdoc

    Carina Goos (2017)

     

    Purification and characterisation of trypanosome nuclear periphery granules

     

    Master Students

    Andrea Reichert (2018)

    Untersuchungen zur Funktion der spezifischen Lokalisation des T. brucei mRNA-Decapping-Enzyms

    Nadja Sauer (2016) 

    In vivo Markierung von mRNAs in RNP Granula durch photoaktivierbare, abstandsabhängige Biotinylierung: Etablierung der Methode

    Hanna Thoma (2016)

    Warum sind für ribosomale Proteine kodierende mRNAs aus Stress-Granula ausgeschlossen?

    Christina Julia Lorenz (2015, extern in Cambridge)

    Identification of interaction partners of the DEAD-box RNA helicase DHH1 in Trypanosoma brucei

    Nina Krienitz (2015, extern Cambridge and Dundee)

    Implementation of a novel cryomilling method to analyse protein and RNA interactions of the poly(A)-binding proteins in Trypanosoma brucei

    Melanie Fritz (2014)

    Zusammensetzung und Ultrastruktur von Stress-Granula in Trypanosoma brucei brucei

    Bachelor Students

    Laura Gauglitz (2018)

    Etablierung einer neuen BioID Methode in Trypanosomen

    Laura Peters (2017)

    Warum sind mRNAs, die für ribosomale Proteine kodieren, aus Stress-Granula ausgeschlossen?

    Till Elharrar (2015)

    Validierung der Lokalisation zu ‘Nuclear periphery granules’ von neu identifizierten Proteinkandidaten

    Nadja Sauer (2014)

    Überprüfung neuer Stressgranula-Protein-Kandidaten in Trypanosoma brucei​​​​​​​

    Daja Schichler (2014)

    Analyse von RNA-Granula in Trypanosoma brucei

    Melanie Fritz (2012)

    Charakterisierung von Stress-Granula in Trypanosoma brucei brucei

    Mario Hofweber (2012)

    Ist das trypanosomale P-body Protein SCD6 ein Multimer?

    Internship

    Frederik Heim

    Corinna Kronenthaler

    Johannes Schmidt

    Bilal Tetik

    Susheela Behera

    FUNDING

    Contact

    Lehrstuhl für Zoologie I - Zell- und Entwicklungsbiologie
    Am Hubland
    97074 Würzburg

    Phone: +49 931 31-84250
    Fax: +49 931 31-84252
    Email

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