Nucleic acid and protein sequences relating to a gene required for systemic RNAi are disclosed. The SID-1 protein is shown to be required for systemic RNAi. Nucleic acids, vectors, transformed cells, transgenic animals, polypeptides, and antibodies relating to the sid-1 gene and protein are disclosed. Also provided are methods for reducing the expression of a target gene in a cell, a population of cells, or an animal.