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Lehrstuhl für Zell- und Entwicklungsbiologie

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

NEWs

RNA 2019

June, 2019

We met with our Polish Collaboraters from the laboratory of Maria Gorna at the RNA society meeting in Krakow. Together we will unravel the secrets of the trypanosome decapping enzyme !

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