LOTUS domains are helix-turn-helix protein folds identified in essential germline proteins and are conserved in prokaryotes and eukaryotes. Despite originally predicted as an RNA binding domain, its molecular binding activity towards RNA and protein is controversial. In particular, the most conserved binding property for the LOTUS domain family remains unknown. Here, we uncovered an unexpected specific interaction of LOTUS domains with G-rich RNA sequences. Intriguingly, LOTUS domains exhibit high affinity to RNA G-quadruplex tertiary structures implicated in diverse cellular processes including piRNA biogenesis. This novel LOTUS domain-RNA interaction is conserved in bacteria, plants and animals, comprising the most ancient binding feature of the LOTUS domain family. By contrast, LOTUS domains do not preferentially interact with DNA G-quadruplexes. We further show that a subset of LOTUS domains display both RNA and protein binding activities. These findings identify the LOTUS domain as a specialized RNA binding domain across phyla and underscore the molecular mechanism underlying the function of LOTUS domain-containing proteins in RNA metabolism and regulation.

中文翻译：

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LOTUS域是一类新颖的富含G和G-四链体RNA结合域。

LOTUS域是必需种系蛋白中鉴定的螺旋-转-螺旋蛋白折叠，在原核生物和真核生物中保守。尽管最初被预测为RNA结合域，但其对RNA和蛋白质的分子结合活性仍存在争议。特别是，LOTUS域家族最保守的结合特性仍然未知。在这里，我们发现了LOTUS域与富含G的RNA序列之间的意外特异性相互作用。有趣的是，LOTUS结构域对包含piRNA生物发生在内的多种细胞过程中涉及的RNA G-四链体三级结构表现出高亲和力。这种新颖的LOTUS域-RNA相互作用在细菌，植物和动物中得以保留，具有LOTUS域家族最古老的结合特征。相比之下，莲花域不优先与DNA G四链体相互作用。我们进一步表明，LOTUS域的子集显示RNA和蛋白质结合活性。这些发现将LOTUS结构域鉴定为跨门的特定RNA结合结构域，并强调了在RNA代谢和调控中含LOTUS结构域蛋白功能的分子机制。