Investigating the effects of pathogen attack on the miRNA machinery. — The Association Specialists
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  3. Investigating the effects of pathogen attack on the miRNA machinery.

Investigating the effects of pathogen attack on the miRNA machinery. (320)

Sarah Bajan 1 , Gyorgy Hutvagner 1
  1. University of Technology Sydney, Ultimo, NSW, Australia

miRNAs mediate eukaryotic gene regulatory mechanisms that target gene expression at post-transcriptional stages. miRNAs exert an extensive influence - they are implicated in many biological pathways and in the development of several diseases, including cancer1. miRNAs have an essential role in human innate and adaptive immune response systems2. As a response to infection, the host cell induces the expression of several miRNAs while several pathogen-derived miRNAs have been identified which function to disrupt the immune response.  Additionally, pathogens target Argonaute proteins, which are essential for miRNA function, altering their function and stability3.  Therefore investigating the regulation of the key components of the miRNA pathway during infection will provide insights into the mechanisms of pathogenesis and potentially could identify novel drug targets.  

We aim to establish a model of infection using a cell based assay. This system will allow us to investigate the response of the human miRNA pathway during an infection.   Furthermore, we will examine the interactions between the host miRNA machinery and pathogen-derived proteins and small RNAs.

Initial studies indicate that the levels of Argonaute protein are altered upon infection, and that this change is mediated at a post-transcriptional stage of expression. Future studies will investigate the role of Argonaute proteins, and other components of the miRNA pathway, for both the host immune response and for successful pathogenesis.

  1. Sotiropoulou, G., Pampalakis, G., Lianidou, E. & Mourelatos, Z. Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell. RNA 15, 1443-61 (2009)
  2. Bi, Y., Liu, G. & Yang, R. MicroRNAs: novel regulators during the immune response. J Cell Physiol 218, 467-72 (2009)
  3. Csorba, T., Lozsa, R., Hutvagner, G. & Burgyan, J. Polerovirus protein P0 prevents the assembly of small RNA-containing RISC complexes and leads to degradation of ARGONAUTE1. Plant J 62, 463-72