DFG Research Group FOR855

    Effect of viral infections on the activity of cellular RNAs

    Prof. Dr. S. Behrens

    Project Summary:

    During earlier work we characterized a set of predominantly nuclear proteins that in cells infected with the positive-strand RNA viruses HCV (human hepatitis C virus) or BVDV (bovine viral diarrhea virus) are sequestered by the viral replication machinery in the cytoplasm. These so-called 'NF/NFAR proteins' bind to RNA motifs in the non-translated regions of both viral genomes, and there is evidence that the proteins support the coordination of viral protein and RNA synthesis. In naive cells, the prototype NF/NFAR protein, NF90/NFAR-1 (ILF3, DRBP76), is known to stabilize certain mRNAs increasing their translation. The intriguing scenario that replicating viral RNAs sequester proteins that regulate the activity of cellular RNAs led to the aim of this application, i.e., to understand whether viral sequestration of NF90/NFAR-1 affects the activity of natural cellular RNA targets of this protein. With these studies we anticipate obtaining insights into how RNA viruses shape cellular gene expression.

    Selected publications (2007-09):

    1 Isken, O., Baroth, M., Grassmann, C.W., Weinlich, S., Ostareck, D.H., Ostareck-Lederer, A. and Behrens, S.-E. (2007). Nuclear factors are involved in hepatitis C virus RNA replication. RNA 13: 1675-1692.

    2   Weinlich, S., Hüttelmaier, S., Schierhorn, A., Behrens, S.-E., Ostareck-Lederer, A., and Ostareck, D.H. (2009). IGF2BP1 enhances HCV IRES-mediated translation initiation via the 3'UTR. RNA 15:1528-42.

    3  Gursinsky, T., Schulz, B., and Behrens, S.-E. (2009). Replication of tomato bushy stunt virus RNA in a plant in vitro system. Virology 390: 250-60.
    4  Heidebrecht, F., Schulz, I., Keller, M., Behrens, S.-E., and Bader, A. (2009). Improved protocols for Protein and RNA Isolation from 3D Collagen Sandwich Cultures of primary Hepatocytes. Anal Biochem. 393: 141-4

    5 Heidebrecht, F., Heidebrecht, A., Schulz, I., Behrens, S.-E., and Bader, A. (2009) Improved semiquantitative Western blot technique with increased quantification range. J Immunol Methods. 345: 40-8.
    Patent applications

    1 Breunig, K., Behrens, S.-E.: Verfahren zur oralen Vakzinierung mittels rekombinanter Hefen. Deutsches Patentamt, Aktz. 10 2008 057 451.1.

    2 Schoenbrunner, R., Behrens, S.-E.: Replication stable and RNase resistant chimeras of pestivirus with insertion in 3' nontranslated region (3'NTR). USPTO, Appl. No. 12277282, 24-Nov-2008