We proposed a scan-RNA model for genome rearrangement based on finding small RNAs that hybridized preferentially to micronuclear-specific sequences and on the properties of Twi1p, a PPD protein required for both sequence elimination and small RNA accumulation in Tetrahymena. Here we show that Twi1p interacts with the small RNAs in both the old and the developing macronucleus, and is required for their stability. We show that the specificity of the small RNAs for micronuclear-limited sequences increases during conjugation. These results indicate that the small RNAs observed in conjugating cells have the properties predicted for scan RNAs.