Repeated evolution of inactive pseudonucleases in a fungal branch of the Dis3/RNase II family of nucleases
Repeated evolution of inactive pseudonucleases in a fungal branch of the Dis3/RNase II family of nucleases
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Dis3/RNase II 核酸酶家族真菌分支中无活性假核酸酶的重复进化
DOI：
10.1101/2020.07.30.229070
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ballou E
中科院分区：
文献类型：
--
作者：
Ballou E
RNase II家族的3′-5′核糖核酸外切酶存在于生命的各个领域，真核生物家族成员Dis 3和Dis 3L 2在RNA降解中起重要作用。子囊菌酵母含有Dis 3和失活的RNA酶II样“核糖核酸酶”。后者作为RNA结合蛋白发挥作用，影响细胞生长、胞质分裂和真菌致病性。然而，这些核糖核酸酶的进化起源是未知的：什么样的事件序列导致了它们的新功能，这些事件是什么时候发生的？在这里，我们展示了如何RNase II核糖核酸酶同源物，包括SaccharomycesParaeSsd 1，是从活性Dis 3L 2酶的后裔。在真菌进化过程中，Dis 3L 2同源物中的活性位点突变至少出现了四次，在某些情况下是在基因重复之后。相比之下，N-末端冷休克结构域和监管功能是保守的不同dikarya和毛霉门，这表明非核酸酶的功能需要这些地区。在担子菌致病性酵母隐球菌neoformans中，从多倍体“泰坦”生长阶段的胞质分裂需要单一的Ssd 1/Dis 3L 2同源物。这种新型隐球菌Ssd 1/Dis 3L 2缺失的表型与无活性真菌内切核酸酶的表型一致，但该蛋白保留了活性位点序列特征。我们建议，一个核酸酶的独立功能的Dis 3L 2出现在一个祖先的菌丝形成真菌。这第二种功能在数亿年的时间里一直保持着，而核糖核酸酶的活性在独立的谱系中反复丢失。
The RNase II family of 3′–5′ exoribonucleases is present in all domains of life, and eukaryotic family members Dis3 and Dis3L2 play essential roles in RNA degradation. Ascomycete yeasts contain both Dis3 and inactive RNase II-like “pseudonucleases.” The latter function as RNA-binding proteins that affect cell growth, cytokinesis, and fungal pathogenicity. However, the evolutionary origins of these pseudonucleases are unknown: What sequence of events led to their novel function, and when did these events occur? Here, we show how RNase II pseudonuclease homologs, includingSaccharomyces cerevisiaeSsd1, are descended from active Dis3L2 enzymes. During fungal evolution, active site mutations in Dis3L2 homologs have arisen at least four times, in some cases following gene duplication. In contrast, N-terminal cold-shock domains and regulatory features are conserved across diverse dikarya and mucoromycota, suggesting that the nonnuclease function requires these regions. In the basidiomycete pathogenic yeastCryptococcus neoformans, the single Ssd1/Dis3L2 homolog is required for cytokinesis from polyploid “titan” growth stages. This phenotype ofC. neoformansSsd1/Dis3L2 deletion is consistent with those of inactive fungal pseudonucleases, yet the protein retains an active site sequence signature. We propose that a nuclease-independent function for Dis3L2 arose in an ancestral hyphae-forming fungus. This second function has been conserved across hundreds of millions of years, whereas the RNase activity was lost repeatedly in independent lineages.