Abstract:
Extensive adenosine-to-inosine (A-to-I) editing of nuclear-transcribed mRNAs is the hallmark of metazoan transcriptional regulation. Here, by profiling the RNA editomes of 22 species that cover major groups of Holozoa, we provide substantial evidence supporting A-to-I mRNA editing as a regulatory innovation originating in the last common ancestor of extant metazoans. This ancient biochemistry process is preserved in most extant metazoan phyla and primarily targets endogenous double-stranded RNA (dsRNA) formed by evolutionarily young repeats. We also find intermolecular pairing of sense-antisense transcripts as an important mechanism for forming dsRNA substrates for A-to-I editing in some but not all lineages. Likewise, recoding editing is rarely shared across lineages but preferentially targets genes involved in neural and cytoskeleton systems in bilaterians. We conclude that metazoan A-to-I editing might first emerge as a safeguard mechanism against repeat-derived dsRNA and was later co-opted into diverse biological processes due to its mutagenic nature.
摘要:
核转录mRNA的广泛的腺苷到肌苷(A到I)编辑是后生动物转录调控的标志。这里,通过分析涵盖Holozoa主要群体的22个物种的RNAeditome,我们提供了大量证据支持A-ImRNA编辑作为一种调控创新,起源于现存后生动物的最后一个共同祖先。这种古老的生物化学过程保存在大多数现存的后生动物门中,主要针对由进化上年轻的重复序列形成的内源性双链RNA(dsRNA)。我们还发现有义-反义转录物的分子间配对是在一些但不是所有谱系中形成用于A到I编辑的dsRNA底物的重要机制。同样,重新编码编辑很少在谱系之间共享,但优先针对双边神经和细胞骨架系统中涉及的基因。我们得出的结论是,后生动物A到I编辑可能首先成为抵抗重复序列来源的dsRNA的保障机制,后来由于其致突变性而被纳入多种生物过程。