Program Nr: 271A

Argonaute-1 gene in Drosophila is required for interconnecting transcriptional gene silencing and viral resistance. U. Bhadra 1, SNCVL. Pushpavalli 1, M. Pal-Bhadra 2. 1) Functional Genomics and Gene silencing Group, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India; 2) Shantha Biotechnology Pvt. Ltd. Hyderabad, India.

   Introduction of hybrid gene causes transcriptional gene silencing (TGS) by recruiting the Polycomb complex at the transgene insertion sites. In contrast, the full length transgenes in higher dosage induces threshold related post transcriptional gene silencing (PTGS) converting mature mRNA to 21-23 nt long dsRNA that guide further destruction of homologous RNA. The down stream steps of PTGS follow mechanistic hallmarks of RNA interference, and are identical to natural viral resistance in plants and animals. A number of RNAi defective mutations are widely conserved in Arabidopsis, C. elegans and Drosophila. One member piwi in Drosophila draws a potential inter-connection between TGS and PTGS. Here, we report other member of Argonautelike gene family, AGO1 mutation blocks some aspects of transcriptional silencing especially non-homologous interaction between Adhwhite and reciprocal white-Adh transgenes. Moreover, we found that small interfering RNAs generated against RNA dependent RNA polymerase gene of Drosophila C Virus (DCV) efficiently reduces viral infection in transgenic flies. DCV infection in general alters several demographic parameters during Drosophila development. The relative changes of several parameters in wild type and in AGO1 mutant background reveals that AGO1 mutation suppresses RNAi based DCV resistance indicating a potential link between transcriptional gene silencing and DCV resistance in Drosophila. The positive effect of AGO1 on TGS and threshold induced PTGS support this view. Alternatively, it is presumed that AGO1 might function at least some overlapping sectors of two types of mechanisms.