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.