MicroRNAs (miRNAs) are a class of small noncoding RNAs that negatively regulates gene expression by destabilization or translational inhibition of mRNAs. miRNAs are encoded in the genome as part of longer primary transcripts and are subsequently processed by two nucleolytic events catalyzed by the RNase III enzymes Drosha and Dicer. The expression of miRNAs is tightly regulated, and in many cases deregulation of miRNA abundance has been linked to diseases including cancer. Apart from transcriptional regulation of the primary miRNAs, it has become evident that also the maturation steps can be specifically regulated by RNA binding proteins. However, only a small number of posttranscriptional miRNA regulators has been discovered to date.

Therefore, we have set up a proteomics-based screen to identify proteins specifically binding to individual miRNA precursors. In the proposed project, we plan to screen a set of 70 miRNAs in a panel of 10 different cancer cell lines in order to identify posttranscriptional miRNA regulators involved in tumorigenesis and tumor progression. Together with rigorous validation experiments, this project will for the first time generate a comprehensive view of posttranscriptional regulation of the biogenesis of individual miRNAs in different cell lines.

Dr. Thomas Treiber

Dr. Nora Treiber

Schraivogel D, Meister G (2014). Import routes and nuclear functions of Argonaute and other small RNA-silencing proteins. Trends Biochem Sci 39(9):420-431.

Hauptmann J, Kater L, Löffler P, Merkl R, Meister G (2014). Generation of catalytic human Ago4 identifies structural elements important for RNA cleavage. RNA 20(10):1532-8.

Chandran PA, Keller A, Weinmann L, Adel Seida A, Braun M, Andreev K, Fischer B, Horn E, Schwinn S, Junker M, Houben R, Dombrowski Y, Dietl J, Finotto S, Wölfl M, Meister G, Wischhusen J (2014). The TGF-β-inducible miR-23a cluster attenuates IFN-γ levels and antigen-specific cytotoxicity in human CD8+ T cells. J Leukoc Biol. [Epub ahead of print]

Hannus M, Beitzinger M, Engelmann JC, Weickert MT, Spang R, Hannus S, Meister G (2014). siPools: highly complex but accurately defined siRNA pools eliminate off-target effects. Nucleic Acids Res 42(12):8049-61.

Loedige I, Stotz M, Qamar S, Kramer K, Hennig J, Schubert T, Löffler P, Längst G, Merkl R, Urlaub H, Meister G (2014). The NHL domain of BRAT is an RNA-binding domain that directly contacts the hunchback mRNA for regulation. Genes Dev 28(7):749-64.

Dueck A, Meister G (2014). Assembly and function of small RNA - argonaute protein complexes. Biol Chem 395(6):611-29. 

Dueck A, Eichner A, Sixt M, Meister G (2014). A miR-155-dependent microRNA hierarchy in dendritic cell maturation and macrophage activation. FEBS Lett 588(4):632-40. 

Pfaff J, Hennig J, Herzog F, Aebersold R, Sattler M, Niessing D, Meister G (2013). Structural features of Argonaute-GW182 protein interactions. Proc Natl Acad Sci U S A 110(40):E3770-9. 

Pfaff J, Meister G (2013). Argonaute and GW182 proteins: an effective alliance in gene silencing. Biochem Soc Trans 41(4):855-60.

Meister G (2013). Argonaute proteins: functional insights and emerging roles. Nat Rev Genet 14(7):447-59. 

Hauptmann J, Dueck A, Harlander S, Pfaff J, Merkl R, Meister G (2013). Turning catalytically inactive human Argonaute proteins into active slicer enzymes. Nat Struct Mol Biol 20(7):814-7. 

Schraivogel D., Weinmann L., Beier D., Tabatabai G., Eichner A., Zhu J.Y., Anton M., Sixt M., Weller M., Beier C. & Meister G. (2011) CAMTA1 is a novel tumor suppressor regulated by miR-9/9* in glioblastoma stem cells, EMBO J., 30(20):4309-22.

Petri S., Dueck A., Lehmann G., Putz N., Rüdel S., Kremmer E. & Meister G. (2011) Increased siRNA duplex stability correlates with reduced off-target and elevated on-target effects. RNA, 17(4):737-49.

Rüdel S., Wang Y., Lenobel R., Körner R., Hsiao H., Urlaub H., Patel D. & Meister G. (2011) Phosphorylation of human Argonaute proteins affects small RNA binding. Nucleic Acids Research, 39(6):2330-2343.

Aguilar A.L., Piskol R., Beitzinger M., Zhu J.Y., Kruspe D., Aszodi A., Moser M., Englert C. & Meister G. (2010) The small RNA expression profile of the developing murine urinary and reproductive systems. FEBS Lett., 584(21):4426-34.

Zhu J.Y., Pfuhl T., Motsch N., Barth S., Nicholls J., Grässer F. & Meister G. (2009) Identification of novel Epstein-Barr Virus microRNA genes from Nasopharyngeal Carcinomas. Journal of Virology, 83(7):3333-41.

Weinmann, L., Höck, J., Ivacevic T., Ohrt T., Mütze J., Schwille P., Kremmer E., Benes V., Urlaub, H., & Meister G. (2009) Importin 8 is a gene silencing factor that targets Argonaute proteins to distinct mRNAs. Cell, 136, 496-507.

Ender C., Krek A., Friedländer M.R., Beitzinger M., Weinmann L., Chen W., Pfeffer S., Rajewsky N. & Meister G. (2008) A human snoRNA with microRNA-like functions. Molecular Cell, 32, 519-528.

Rüdel S., Flatley A., Weinmann L., Kremmer E. & Meister G. (2008) A multifunctional human Argonaute2-specific monoclonal antibody. RNA, 14, 1244-1253.

Höck J., Peters L., Ender C., Rüdel S., Kremmer E., Urlaub H. & Meister G. (2007) Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells. EMBO Reports, 8, 11, 1052-1060.

Beitzinger M., Peters L., Zhu J. Y., Kremmer E. & Meister G. (2007) Identification of microRNA targets from isolated Argonaute protein complexes. RNA Biology, 4(2).

Chen P. Y., Weinmann L., Gaidatzis D., Pei Y., Zavolan M., Tuschl T. & Meister G. (2007) Strand-specific 5’-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity. RNA, 14, 1-12.

The company siTools Biotech GmbH, which was co-founded by Prof. Gunter Meister, was recently awarded the 2nd price in the business plan contest Nordbayern 2014. The contest is organized by the innovation and entrepreneurship initiative "Netzwerk Nordbayern" in cooperation with Siemens AG. The video of the award-winning project titled "new reagents for gene function analyis" is shown below. Read more in the official press release of the University of Regensburg. Congratulations to Prof. Gunter Meister and siTools Biotech GmbH!