A comprehensive analysis of the La-motif protein superfamily
A comprehensive analysis of the La-motif protein superfamily
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DOI：
10.1261/rna.1478709
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发表时间：
2009-05-01
期刊：
影响因子：
4.5
通讯作者：
Deragon, Jean-Marc
中科院分区：
文献类型：
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作者：
Bousquet-Antonelli, Cecile;Deragon, Jean-Marc
极其保守的 La 基序 (LAM) 与紧随其后的 RNA 识别基序 (RRM) 协同作用，允许（真正的）La 自身抗原与 RNA 聚合酶 III 初级转录物直接结合。该基序不仅存在于 La 同系物上，而且也存在于功能无关的 La 相关蛋白 (LARP) 上。 LARP 广泛存在于真核生物中，尽管其特征尚不明确，但似乎是实现关键细胞功能的 RNA 结合蛋白。我们搜索了分布在生命树上的 83 个真核物种的完整测序基因组，以寻找含有 LAM 的蛋白质的存在。我们观察到这些蛋白质在古细菌中不存在，但存在于所有真核生物中（疟原虫属的原生生物除外），强烈表明 LAM 是古细菌-真核辐射后早期出现的祖先基序。对这些蛋白质的完整进化和结构分析将其分为五个家族：真正的 La 同系物和四个 LARP 家族。出乎意料的是，在每个家族中，代表经典 RRM 或 RRM 样基序的保守结构域紧跟在大多数蛋白质的 LAM 之后。 LAM-RRM/RRM-L 区域的进化分析表明，这些基序共同进化，并且应该用作单个实体来定义 LARP 与其底物相互作用的功能区域。我们还发现了两个极其保守的基序，名为 LSA 和 DM15，分别由 LARP6 和 LARP1 家族成员共享。我们认为同一家族的成员是功能同系物和/或对不同 RNA 诱饵具有共同的分子作用模式。
The extremely well-conserved La motif (LAM), in synergy with the immediately following RNA recognition motif (RRM), allows direct binding of the (genuine) La autoantigen to RNA polymerase III primary transcripts. This motif is not only found on La homologs, but also on La-related proteins (LARPs) of unrelated function. LARPs are widely found amongst eukaryotes and, although poorly characterized, appear to be RNA-binding proteins fulfilling crucial cellular functions. We searched the fully sequenced genomes of 83 eukaryotic species scattered along the tree of life for the presence of LAM-containing proteins. We observed that these proteins are absent from archaea and present in all eukaryotes (except protists from the Plasmodium genus), strongly suggesting that the LAM is an ancestral motif that emerged early after the archaea-eukarya radiation. A complete evolutionary and structural analysis of these proteins resulted in their classification into five families: the genuine La homologs and four LARP families. Unexpectedly, in each family a conserved domain representing either a classical RRM or an RRM-like motif immediately follows the LAM of most proteins. An evolutionary analysis of the LAM-RRM/RRM-L regions shows that these motifs co-evolved and should be used as a single entity to define the functional region of interaction of LARPs with their substrates. We also found two extremely well conserved motifs, named LSA and DM15, shared by LARP6 and LARP1 family members, respectively. We suggest that members of the same family are functional homologs and/or share a common molecular mode of action on different RNA baits.