Poster Presentation Lorne Infection and Immunity 2019

Regulation of alternative splicing in Plasmodium falciparum (#158)

Emma McHugh 1 , Lee M Yeoh 1 , Vern Lee 1 , Simon Cobbold 1 , Stuart Ralph 1
  1. University of Melbourne, Parkville, VIC, Australia

The malaria parasite, Plasmodium falciparum, undergoes significant morphological changes throughout its lifecycle stages. Accordingly, transcription of genes in P. falciparum is tightly regulated in a stage-dependent manner. These transcriptional changes have been described by numerous RNA-seq studies and several key transcription factors have now been identified. However, post-transcriptional control of gene expression has been less-well characterised in the malaria parasite. Alternative splicing of mRNA can produce transcripts of varying stability and is a method of post-transcriptional control of expression. In mammals, alternative splicing has been shown to be important for differentiation of cells. We are interested in investigating alternative splicing as a mechanism of parasite differentiation during its lifecycle. To achieve this, we are investigating the putative mediators of alternative splicing in P. falciparum: SR proteins and SR protein kinases. The SR proteins are RNA-binding proteins that can regulate the association of the spliceosome with mRNA. The localisation and activity of SRs is regulated by the SR protein kinases. We have used a CRISPR approach to create epitope-tagged, inducible knockdown/knockout parasite lines for six different SR proteins and three SR protein kinases. We have determined the subcellular localisation of each of these proteins and are investigating blood-stage development of the parasite after perturbation of these splicing regulators.