Processive Recoding and Metazoan Evolution of Selenoprotein P: Up to 132 UGAs in Molluscs
Processive Recoding and Metazoan Evolution of Selenoprotein P: Up to 132 UGAs in Molluscs
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DOI：
10.1016/j.jmb.2019.08.007
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发表时间：
2019-11-08
影响因子：
5.6
通讯作者：
Atkins, John F.
中科院分区：
文献类型：
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作者：
Baclaocos, Janinah;Santesmasses, Didac;Atkins, John F.
硒蛋白通常含有一个硒代半胱氨酸，即第 21 个氨基酸，由上下文重新定义的 UGA 编码。然而，人硒蛋白 P (SelenoP) 在其 N 端结构域中具有氧化还原功能的硒代半胱氨酸，在其 C 端结构域中具有九个具有硒转运蛋白功能的硒代半胱氨酸。在这里，我们表明，多种 SelenoP 基因存在于具有高度可变数量的 Sec-UGA 的后生动物中，范围从某些昆虫中的单个 UGA，到普通蜘蛛中的 9 个，以及双壳类软体动物中的多达 132 个。 SelenoP 基因是由与硒使用相关的动态进化过程形成的。基因进化的特点是祖先多 Sec 结构域的模块化扩展，这导致许多水生生物中产生了特别富含 Sec 的 SelenoP 蛋白。我们以软体动物为研究对象，选择太平洋牡蛎 Magallana gigas 作为实验模型。我们证明具有 46 个 UGA 的牡蛎 SelenoP mRNA 在体内可全长翻译。核糖体分析表明，硒代半胱氨酸特异性在 UGA1 处的效率接近 5%，而在远端 3' UGA 处的效率接近 100%。我们报告了与其表达相关的遗传元件，包括前导开放阅读框和与起始密码子重叠的RNA结构，以硒依赖性方式调节核糖体进展。与哺乳动物的对应物不同，牡蛎 SelenoP 中的两个 SECIS 元件（3'UTR 重新编码元件）在体外不显示功能分化。补充牡蛎后，其组织硒水平可增加高达 50 倍，这也会导致硒蛋白表达的广泛变化。 (C) 2019 作者。由爱思唯尔有限公司出版
Selenoproteins typically contain a single selenocysteine, the 21st amino acid, encoded by a context-redefined UGA. However, human selenoprotein P (SelenoP) has a redox-functioning selenocysteine in its N-terminal domain and nine selenium transporter-functioning selenocysteines in its C-terminal domain. Here we show that diverse SelenoP genes are present across metazoa with highly variable numbers of Sec-UGAs, ranging from a single UGA in certain insects, to 9 in common spider, and up to 132 in bivalve molluscs. SelenoP genes were shaped by a dynamic evolutionary process linked to selenium usage. Gene evolution featured modular expansions of an ancestral multi-Sec domain, which led to particularly Sec-rich SelenoP proteins in many aquatic organisms. We focused on molluscs, and chose Pacific oyster Magallana gigas as experimental model. We show that oyster SelenoP mRNA with 46 UGAs is translated full-length in vivo. Ribosome profiling indicates that selenocysteine specification occurs with similar to 5% efficiency at UGA1 and approaches 100% efficiency at distal 3' UGAs. We report genetic elements relevant to its expression, including a leader open reading frame and an RNA structure overlapping the initiation codon that modulates ribosome progression in a selenium-dependent manner. Unlike their mammalian counterparts, the two SECIS elements in oyster SelenoP (3'UTR recoding elements) do not show functional differentiation in vitro. Oysters can increase their tissue selenium level up to 50-fold upon supplementation, which also results in extensive changes in selenoprotein expression. (C) 2019 The Author(s). Published by Elsevier Ltd.