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Göran Akusjärvi

Research Focus

We are using human DNA viruses as model systems to decipher basic regulatory mechanism controlling gene expression at the level of RNA biogenesis and RNA processing. In this work we have shown that the SR family of splicing factors are key targets during many virus infections (adenovirus, herpes virus and vaccinia virus). We have shown that adenovirus reprograms the cellular splicing machinery to preferentially splice virus-specific RNAs by inducing a PP2A-dependent dephosphorylation of the SR family of proteins. A key finding from our work was the demonstration of the Janus nature of SR proteins - i.e. they can functions as activators or repressors of splicing dependent on where on the pre-mRNA they bind. We have also shown that splicing of certain pre-mRNAs in adenovirus-infected cells occurs in the absence of the general splicing factor U2AF. Further, this U2AF-independent splicing appears to require a novel type of virus-encoded splicing enhancer, a splicing enhancer that is only functional in the context of an adenovirus-infected cell. Our current research is focused on a novel viral protein, which is a candidate protein taking over the function of U2AF in virus-infected cells. This protein is an alternative splicing factor that appears to be the only viral protein necessary to convert a HeLa cell to a cell with splicing properties similar to a virus-infected cell.

Publications

  1. Andersson, G., Xu, N., Akusjärvi, G. (2007). In vitro methods to study RNA interference during an adenovirus infection. Methods in Molecular Medicine 131, 47-61.
  2. Kvissel, A.K., Ørstavik, S., Eikvar, S., Brede, G., Jahnsen, T., Collas, P., Akusjärvi, G., Skålhegg, B.S. (2007). Involvement of the catalytic subunit of protein kinase A and of HA95 in pre-mRNA splicing. Experimental Cell Research 313(13), 2795-809.
  3. Xu, N., Segerman, B., Zhou, X., Akusjärvi, G. (2007). Adenovirus virus-associated RNAII-derived small RNAs are efficiently incorporated into the rna-induced silencing complex and associate with polyribosomes. Journal of Virology 81(19), 10540-9.
  4. Mühlemann, O., Akusjärvi, G. (2007). Preparation of soluble extracts from adenovirus-infected cells for studies of RNA splicing. Methods in Molecular Medicine 131, 33-46.
  5. Törmänen, H., Backström, E. Carlsson, A., and Akusjärvi, G. (2006). L4-33K, an adenovirus encoded alternative RNA splicing factor. Journal of Biological Chemistry 281, 36510-36517.
  6. Öhrmalm, C. and Akusjärvi, G. (2006). The cellular splicing/transcription regulatory protein p32 represses adenovirus major late transcription unit and causes RNA polymerase II hyperphosphorylation. Journal of Virology 80, 5010-5020.
  7. Lützelberger, M. Backström, E. and Akusjärvi, G. (2005). Substrate dependent differences in U2AF requirement for splicing in adenovirus-infected cell extracts. Journal of Biological Chemistry 280, 25478-25484.
  8. Dauksaite, V. and Akusjärvi, G. (2002). Human splicing factor ASF/SF2 encodes for a repressor domain required for its inhibitory activity on pre-mRNA splicing. Journal of Biological Chemistry 277, 12579-12586.
  9. Estmer, C., Petersen-Mahrt, S., Durot, C., Strichtman, S., Krainer, A., Kleinberger, T. and Akusjärvi, G. (2001). The adenovirus E4-ORF4 splicing enhancer protein interacts with a subset of phosphorylated SR proteins. EMBO Journal 20, 864-871.
  10. Kanopka, A., Mühlemann, O., Petersen-Mahrt, S., Estmer, C., Öhrmalm, C. and Akusjärvi, G. (1998). Regulation of adenovirus alternative RNA splicing by dephosphorylation of SR proteins. Nature 393, 185-187.

Key lab techniques: Nuclear extract preparation, in vitro splicing, virus infection, transient transfection, in vivo reporter gene analysis (CAT, Luc, S1, RT-PCR, Northern, Western), construction of recombinant adenovirus vectors, ChIP analysis.

Lab contact: goran.akusjarvi@imbim.uu.se