Figure 1.

The RuNAway disease scheme. In the primary latent cycle (blue), a clone of SINE genes gradually escapes from the default state of heavily suppressed replication. Sources of new mutations (orange) are provided by RNA Pol. III and the error-prone reverse transcriptase. Mutations that improve retroposition competence are iteratively incorporated into new genes, leading to shorter cycle times. As newly inserted SINE genes proliferate, SINE RNA concentration increases, which may be aided by mutations that hinder SINE RNA turnover. A new infection by an aggressively replicating SINE variant will result in rapid cycles of gene proliferation and a shorter latent period. Eventually, SINE RNAs begin to titrate out the cellular pool of PKR, causing the initiation of the secondary virulent cycle (red). Overproduction of PrP protein leads to PrPSc deposits that stress the cell. In turn this induces massive transcription of inherited SINE genes, ensuring that PKR remains fully inhibited. The double positive feedback nature of the virulent cycle ensures that it will only be terminated by cell death.

Gibson Genome Biology 2001 2:preprint0006.1-preprint0006.17   doi:10.1186/gb-2001-2-7-preprint0006