PRMT1 methylates the single Argonaute of Toxoplasma gondii and is important for the recruitment of Tudor nuclease for target RNA cleavage

Cell Microbiol. 2012 Feb 6. doi: 10.1111/j.1462-5822.2012.01763.x. [Epub ahead of print]

PRMT1 methylates the single Argonaute of Toxoplasma gondii and is important for the recruitment of Tudor nuclease for target RNA cleavage by antisense guide RNA.

Musiyenko A, Majumdar T, Andrews J, Adams B, Barik S.

Source
Department of Biochemistry and Molecular Biology, University of South Alabama, College of Medicine, 307 University Blvd., Mobile, Alabama, USA. Center for Gene Regulation in Health and Disease, and Department of Biological, Geological and Environmental Sciences, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, Ohio 44115, USA.

Abstract
Argonaute (Ago) plays a central role in RNA interference in metazoans, but its status in lower organisms remains ill-defined. We report on the Ago complex of the unicellular protozoan, Toxoplasma gondii (Tg), an obligatory pathogen of mammalian hosts. The PIWI-like domain of TgAgo lacked the canonical DDE/H catalytic triad, explaining its weak target RNA cleavage activity. However, TgAgo associated with a stronger RNA slicer, a Tudor staphylococcal nuclease (TSN), and with a protein Arg methyl transferase, PRMT1. Mutational analysis suggested that the N-terminal RGG-repeat domain of TgAgo was methylated by PRMT1, correlating with the recruitment of TSN. The slicer activity of TgAgo was Mg(+2) -dependent and required perfect complementarity between the guide RNA and the target. In contrast, the TSN activity was Ca(+2) -dependent and required an imperfectly paired guide RNA. Ago knockout parasites showed essentially normal growth, but in contrast, the PRMT1 knockouts grew abnormally. Chemical inhibition of Arg methylation also had an anti-parasitic effect. These results suggest that the parasitic PRMT1 plays multiple roles, and its loss affects the recruitment of a more potent second slicer to the paras. © 2012 Blackwell Publishing Ltd.

© 2012 Blackwell Publishing Ltd.

PMID: 22309152 [PubMed - as supplied by publisher]