Regulation of RNA-binding protein stability and function by PRMT7-dependent arginine methylation in Leishmania

Wed11  Apr10:15am(15 mins)
Where:
Stream 1 - Edward Llwyd 0.26 Biology Main
Session:

Authors

T R Ferreira3; A A Dowle2; E V Alves-Ferreira3; T R Larson2; A K Cruz1; P B Walrad3
1 University of São Paulo, Brazil;  2 University of York, UK;  3 University of York, Centre for Immunology and Infection, UK

Discussion

Protein aRginine MethylTransferases (PRMTs) catalyse arginine methylation in various cellular processes. The chromatin modifier PRMT7 is the only Type III PRMT found in higher eukaryotes and a restricted number of unicellular eukaryotes. Leishmania major PRMT7 is a cytoplasmic protein implicit in pathogenesis with unknown substrates. Using comparative methyl-SILAC proteomics for the first time in protozoa, we identified 40 putative targets, including 17 RNA-binding proteins (RBPs) hypomethylated in PRMT7 null mutants. In vitro, PRMT7 can modify RBPs Alba3 and RBP16 as direct substrates. In vivo PRMT7 knockout reduces both RBP16 protein half-life and Alba3 mRNA-binding capacity. RNA immunoprecipitation (RIP) analyses demonstrate PRMT7-dependent methylation promotes Alba3 association with target transcripts and consequent stability of delta-amastin surface antigen. These results highlight a novel role for PRMT7-mediated arginine methylation of RBP substrates, suggesting a post-translationally-directed regulatory pathway controlling gene expression and virulence in Leishmania. This work introduces Leishmania PRMTs as epigenetic regulators of mRNA metabolism with novel mechanistic insight into the functional manipulation of RBPs by methylation.

Schedule

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British Society for Parasitology (BSP)
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