Cloning of a protein arginine methyltransferase PRMT1 homolog from Schistosoma mansoni: Evidence for roles in nuclear receptor signaling and RNA metabolism q,qq Jose ´ Joa˜o Mansure a,1 , Daniel Rodrigues Furtado a,1 , Francisco Meirelles Bastos de Oliveira a , Franklin David Rumjanek a , Glo´ria Regina Franco b , Marcelo Rosado Fantappie ´ a, * a Instituto de Bioquı ´ mica Me ´ dica, Universidade Federal do Rio de Janeiro, Ilha do Funda ˜o, Rio de Janeiro 21941-590, Brazil b Departamento de Bioquı ´micae Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 30161-970, Brazil Received 21 July 2005 Available online 11 August 2005 Abstract The most studied arginine methyltransferase is the type I enzyme, which catalyzes the transfer of an S-adenosyl- L -methionine to a broad spectrum of substrates, including histones, RNA-transporting proteins, and nuclear hormone receptor coactivators. We cloned a cDNA encoding a protein arginine methyltransferase in Schistosoma mansoni (SmPRMT1). SmPRMT1 is highly ho ogous to the vertebrate PRMT1 enzyme. In vitro methylation assays showed that SmPRMT1 recombinant protein was able cifically methylate histone H4. Two schistosome proteins likely to be involved in RNA metabolism, SMYB1 and SmSmD3, that display a number of RGG motifs, were strongly methylated by SmPRMT1. In vitro GST pull-down assays showed that SMYB and SmSmD3 physically interacted with SmPRMT1. Additional GST pull-down assay suggested the occurrence of a ternary plex including SmPRMT1, SmRXR1 nuclear receptor, and the p160 (SRC-1) nuclear receptor coactivator. Together, these d gest a mechanism by which SmPRMT1 plays a role in nuclear receptor-mediated chromatin remodeling and RNA transactio 2005 Elsevier Inc. All rights reserved. Keywords: Methylation; Methyltransferase; Gene regulation by nuclear receptors; RNA transport; RNA splicing Schistosoma mansoni is the main causative agent of schistosomiasis, a debilitating disease that still affects millionsof people worldwide [1]. Besidesits medical importance, this parasite constitutes an important mod- el to study sexual differentiation and development, gene regulation, and host–parasite interplay. As part of an ef- fort to understand the molecular aspects of sexual devel- opment in S. mansoni, we have been focusing our studies on the mechanisms of gene expression in the parasite. Transcriptional regulation in eukaryotes encompass- es multiple processes including chromatin reorganiza- tion, processing of pre-mRNA transcripts, and export of the mRNA into the cytoplasm and translation. Activation of transcription at the promoter of a gene involves the binding of transcriptional activator proteins to specific DNA sequences in the promoter. The DNA- bound transcriptional activatorprotein eitherbrings with it or subsequently recruits severalcomplexesof 0006-291X/$ - see front matter 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2005.07.192 q Note: Nucleotide sequence data reported in this paper are available under GenBank Accession No. DQ068274. qq Abbreviations: snRNP, small nuclear ribonucleoprotein; SmSmD3, S. mansoni spliceosome Sm protein D3; PRMT1, protein arginine methyltransferase 1; SRC-1, steroid receptorcoactivator-1;GST, glutathione S-transferase; MBP, maltose-binding protein; SmRXR1, S. mansoni retinoid X receptor 1. * Corresponding author. Fax: +55 21 25612936. E-mail address: fantappie@bioqmed.ufrj.br (M.R. Fantappie ´). 1 These two authors contributed equally to this work. www.elsevier.com/locate/ybbrc Biochemical and Biophysical Research Communications 335 (2005) 1163–1172 BBRC