The association of a La module with the PABP-interacting motif PAM2 is a recurrent evolutionary process that led to the neofunctionalization of La-related proteins
The association of a La module with the PABP-interacting motif PAM2 is a recurrent evolutionary process that led to the neofunctionalization of La-related proteins
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DOI：
10.1261/rna.035469.112
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发表时间：
2013-01-01
期刊：
影响因子：
4.5
通讯作者：
Deragon, Jean-Marc
中科院分区：
文献类型：
--
作者：
Merret, Remy;Martino, Luigi;Deragon, Jean-Marc
La相关蛋白（LARP）在很大程度上是未表征的因子，在整个进化过程中都得到了很好的保守。最近关于人类 LARP4 和 LARP6 功能的报告表明，这些蛋白质在 mRNA 代谢和/或翻译中发挥关键功能。我们在这里报告了真核生物中 LARP4 和 6 家族的详细进化史。编码 LARP4 和 6 的基因在脊椎动物谱系的共同祖先中复制，但一个 LARP6 基因随后在真兽谱系的共同祖先中丢失。 LARP6 基因也在维管植物谱系中独立复制了数次。我们观察到脊椎动物 LARP4 和植物 LARP6 重复事件与 PABP 相互作用基序 2 (PAM2) 的获得及其 RNA 结合模块的显着重组相关。使用等温滴定量热法 (ITC) 和免疫沉淀方法，我们发现两种含有 PAM2 的植物 LARP6（LARP6b 和 c）确实可以与主要植物多聚腺苷酸结合蛋白 (PAB2) 相互作用，而第三种植物 LARP6 (LARP6a) 则不能这样做。我们还分析了两种植物 LARP6 蛋白的 RNA 结合特性和亚细胞定位，发现它们表现出非冗余特征。总的来说，我们的结果支持一个模型，其中 LARP4 和 LARP6 获得 PAM2 允许它们靶向 mRNA 3' UTR 并导致它们的新功能化。
La-related proteins (LARPs) are largely uncharacterized factors, well conserved throughout evolution. Recent reports on the function of human LARP4 and LARP6 suggest that these proteins fulfill key functions in mRNA metabolism and/or translation. We report here a detailed evolutionary history of the LARP4 and 6 families in eukaryotes. Genes coding for LARP4 and 6 were duplicated in the common ancestor of the vertebrate lineage, but one LARP6 gene was subsequently lost in the common ancestor of the eutherian lineage. The LARP6 gene was also independently duplicated several times in the vascular plant lineage. We observed that vertebrate LARP4 and plant LARP6 duplication events were correlated with the acquisition of a PABP-interacting motif 2 (PAM2) and with a significant reorganization of their RNA-binding modules. Using isothermal titration calorimetry (ITC) and immunoprecipitation methods, we show that the two plant PAM2-containing LARP6s (LARP6b and c) can, indeed, interact with the major plant poly(A)-binding protein (PAB2), while the third plant LARP6 (LARP6a) is unable to do so. We also analyzed the RNA-binding properties and the subcellular localizations of the two types of plant LARP6 proteins and found that they display nonredundant characteristics. As a whole, our results support a model in which the acquisition by LARP4 and LARP6 of a PAM2 allowed their targeting to mRNA 3' UTRs and led to their neofunctionalization.