RNA interference (RNAi) was initially discovered as a post-transcriptional gene silencing mechanism in which short RNAs are used to target complementary RNAs for degradation. During the past several years, it has been demonstrated that RNAi-related processes are also involved in transcriptional gene silencing by directing formation of heterochromatin. The dynamic DNA rearrangement during sexual reproduction of the ciliated protozoan Tetrahymena provides an extreme example of RNAi-directed heterochromatin formation. In this process, small RNAs of ∼28-29 nt, which are processed by the Dicer-like protein Dcl1p and are associated with the Argonaute family protein Twi1p, induce heterochromatin formation at complementary genomic sequences by recruiting the histone H3 lysine 9/27 methyltransferase Ezl1p and chromodomain proteins. Eventually these heterochromatinized regions are targeted for DNA elimination. In many eukaryotes, one of the major roles for RNAi-related mechanisms is silencing transposons, and DNA elimination in Tetrahymena is also believed to have evolved as a transposon defense by removing transposon-related sequences from the somatic genome. Because DNA elimination is achieved by the coordinated actions of noncoding RNA transcription, RNA processing, RNA transport, RNA-RNA and RNA-protein interactions, RNA degradation and RNA-directed chromatin modifications, DNA elimination in Tetrahymena is a useful model to study 'RNA infrastructure'.