ADAR-mediated tolerance and SOS splicing-mediated excision of transposable elements

Transposable elements (TEs) threaten genomic integrity, yet their pervasive presence indicates the limitations of existing silencing mechanisms. A recent paper in <i>Nature</i> (Zhao <i>et al</i>. 2025) discovered the SOS splicing system, which provides an RNA-level defense that excises DNA transposons from mRNAs, thereby restoring gene sequence. This spliceosome-independent pathway, mediated by AKAP17A, CAAP1, and RTCB, recognizes dsRNA hairpins formed by inverted terminal repeats (ITRs) and religates the resulting RNA fragments. From an evolutionary perspective, SOS splicing exemplifies a post-transcriptional error-correction mechanism that mitigates the deleterious consequence of TE insertions, paralleling the Constructive Neutral Evolution (CNE) framework. In contrast, ADAR-mediated A-to-I RNA editing suppresses the MDA5-triggered innate immune responses to TE-derived dsRNAs, effectively tolerating rather than eliminating TEs. There may be partial overlap between ADAR and SOS substrates. ADAR editing may delay but not prevent SOS splicing, while SOS excision removes ADAR substrates. The lethality of ADAR loss underscores its role as the mechanism mitigating purifying selection on TEs and thus may contribute to their genomic tolerance and proliferation. Collectively, while ADAR masks the harm of TEs, SOS splicing actively repairs the resulting damage, together illustrating a delicate evolutionary balance between TE tolerance and transcriptomic rescue.