An RNA Splicing System that Excises DNA Transposons from Animal mRNAs [Nanopore]

All genomes harbor mobile genetic parasites called transposable elements (TEs). Here we describe a system, which we term SOS splicing, that protects C. elegans and human genes from DNA transposon-mediated disruption by excising these TEs from host mRNAs. SOS splicing, which appears to operate independently of the spliceosome, is a pattern recognition system triggered by base-pairing of inverted terminal repeat elements, which are a defining feature of DNA transposons. We identify three factors required for SOS splicing in both C. elegans and human cells; AKAP17A, which binds TE-containing mRNAs; the RNA ligase RTCB; and CAAP1, which bridges RTCB and AKAP17A, allowing RTCB to ligate mRNA fragments generated by TE excision. We propose that SOS splicing is a novel, conserved, and RNA structure-directed mode of mRNA splicing and that one function of SOS splicing is to genetically buffer animals from the deleterious effects of DNA-transposon-mediated gene perturbation. Overall design: Nanopore long-read sequencing to characterize SOS splicing isoforms in C. elegans and HEK293T cell line.

所有基因组均携带有一类被称为转座因子（transposable elements, TEs）的可移动遗传寄生因子。本研究描述了一套我们命名为SOS剪接（SOS splicing）的系统，该系统可通过从宿主mRNA中切除此类转座因子，使秀丽隐杆线虫（C. elegans）与人类基因免受DNA转座子介导的基因破坏。SOS剪接似乎不依赖于剪接体（spliceosome）运作，是一类由反向末端重复序列（inverted terminal repeat elements）的碱基配对所触发的模式识别系统，而反向末端重复序列正是DNA转座子的标志性特征。本研究在秀丽隐杆线虫与人类细胞中鉴定出了SOS剪接所需的三种因子：结合含转座因子mRNA的AKAP17A、RNA连接酶RTCB，以及桥接RTCB与AKAP17A、使RTCB能够连接转座因子切除后产生的mRNA片段的CAAP1。我们提出，SOS剪接是一种全新的、保守的、且由RNA结构定向的mRNA剪接模式，其功能之一是为生物体提供遗传缓冲，使其免受DNA转座子介导的基因扰动所带来的有害影响。实验整体设计：采用纳米孔长读长测序技术，对秀丽隐杆线虫与HEK293T细胞系中的SOS剪接异构体进行表征。