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, Janzen CJ, Butter F and Kramer S (2017) The nuclear proteome of Trypanosoma brucei. PLoS One, in press

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

Kramer S, Piper S, Estevez AM & Carrington M (2016) Polycistronic trypanosome mRNAs are a target for the exosome. Mol Biochem Parasitol 205: 1–5

Kramer S (2016) Simultaneous detection of mRNA transcription and decay intermediates by dual colour single mRNA FISH on subcellular resolution. Nucleic Acids Res 45: e49

Fritz M, Vanselow J, Sauer N, Lamer S, Goos C, Siegel TN, Subota I, Schlosser A, Carrington M & Kramer S (2015) Novel insights into RNP granules by employing the trypanosome's microtubule skeleton as a molecular sieve. Nucleic Acids Res 43: 8013–8032

Kramer S & Carrington M (2014) An AU-rich instability element in the 3'UTR mediates an increase in mRNA stability in response to expression of a dhh1 ATPase mutant. translation 2: e28587

Kramer S (2014) RNA in development: how ribonucleoprotein granules regulate the life cycles of pathogenic protozoa. WIREs RNA 5: 263–284

Kramer S, Bannerman-Chukualim B, Ellis L, Boulden EA, Kelly S, Field MC & Carrington M (2013) Differential Localization of the Two T. brucei Poly(A) Binding Proteins to the Nucleus and RNP Granules Suggests Binding to Distinct mRNA Pools. PLoS ONE 8: e54004

Krüger T, Hofweber M & Kramer S (2013) SCD6 induces ribonucleoprotein granule formation in trypanosomes in a translation-independent manner, regulated by its Lsm and RGG domains. Mol Biol Cell 24: 2098–2111

Schwede A, Kramer S & Carrington M (2012) How do trypanosomes change gene expression in response to the environment? Protoplasma 249: 223–238

Kramer S, Marnef A, Standart N & Carrington M (2012) Inhibition of mRNA maturation in trypanosomes causes the formation of novel foci at the nuclear periphery containing cytoplasmic regulators of mRNA fate. J Cell Sci 125: 2896–2909

 

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

The exit of an mRNA molecule from the nucleus needs a tight control system, to prevent the production of aberrant proteins. How is this achieved?

 

Kontakt

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

Tel.: +49 931 31-84250
Fax: +49 931 31-84252
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