Plasmodium falciparum Tudor Staphylococcal Nuclease (PfTSN) has a multidomain organization and preferentially cleaves single stranded RNAs. PfTSN is quite distinct from its vertebrate homologues both in terms of its primary sequence and functional activity. Here, we analyzed the effect of PfTSN specific siRNA on parasite growth and development. Treatment of parasite culture with PfTSN siRNA at the late ring stage resulted in substantial inhibition in parasite growth. The PfTSN siRNA treated parasite cultures showed significant reduction in specific mRNA and PfTSN expression. Morphological examination of PfTSN siRNA treated parasites showed block in the development of parasite at the trophozoite stage. Treatment of parasites with a specific inhibitor of micrococcal nucleases, 3',5'-deoxythymidine biphosphate (pdTp) resulted in similar block in parasite development, thereby suggesting that PfTSN plays an important role at the trophozoite stage of the parasite. Collectively, our findings point towards an essential role for the PfTSN in the parasite's infection cycle. (C) 2008 Elsevier Inc. All rights reserved.