Recognizing the enemy within: licensing RNA-guided genome defense

•How transposons are recognized by RNAi-based mechanisms is poorly understood.•Transcription of some transposons produces dsRNA substrates for Dicer.•Transposon DNA arrangement and chromatin context can also license RNA silencing.•Defective RNA processing signals encoded by transposons can promote RNA silencing. How do cells distinguish normal genes from transposons? Although much has been learned about RNAi-related RNA silencing pathways responsible for genome defense, this fundamental question remains. The literature points to several classes of mechanisms. In some cases, double-stranded RNA (dsRNA) structures produced by transposon inverted repeats or antisense integration trigger endogenous small interfering RNA (siRNA) biogenesis. In other instances, DNA features associated with transposons – such as their unusual copy number, chromosomal arrangement, and/or chromatin environment – license RNA silencing. Finally, recent studies have identified improper transcript processing events, such as stalled pre-mRNA splicing, as signals for siRNA production. Thus, the suboptimal gene expression properties of selfish elements can enable their identification by RNA silencing pathways.