Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston MA 02115, USA.
Nucleic Acids Res. 2013 Aug;41(14):6952-9. doi: 10.1093/nar/gkt409. Epub 2013 May 28.
It is thought that the SelenoCysteine Insertion Sequence (SECIS) element and UGA codon are sufficient for selenocysteine (Sec) insertion. However, we found that UGA supported Sec insertion only at its natural position or in its close proximity in mammalian thioredoxin reductase 1 (TR1). In contrast, Sec could be inserted at any tested position in mammalian TR3. Replacement of the 3'-UTR of TR3 with the corresponding segment of a Euplotes crassus TR restricted Sec insertion into the C-terminal region, whereas the 3'-UTR of TR3 conferred unrestricted Sec insertion into E. crassus TR, in which Sec insertion is normally limited to the C-terminal region. Exchanges of 3'-UTRs between mammalian TR1 and E. crassus TR had no effect, as both proteins restricted Sec insertion. We further found that these effects could be explained by the use of selenoprotein-specific SECIS elements. Examination of Sec insertion into other selenoproteins was consistent with this model. The data indicate that mammals evolved the ability to limit Sec insertion into natural positions within selenoproteins, but do so in a selenoprotein-specific manner, and that this process is controlled by the SECIS element in the 3'-UTR.
人们认为硒代半胱氨酸插入序列（SECIS）元件和 UGA 密码子足以进行硒代半胱氨酸（Sec）的插入。然而，我们发现 UGA 仅在其天然位置或在哺乳动物硫氧还蛋白还原酶 1（TR1）的附近支持 Sec 的插入。相比之下，Sec 可以在哺乳动物 TR3 的任何测试位置插入。将 TR3 的 3'-UTR 替换为 Euplotes crassus TR 的相应片段，将 Sec 插入限制在 C 末端区域，而 TR3 的 3'-UTR 则赋予 E. crassus TR 不受限制的 Sec 插入，在 E. crassus TR 中，Sec 插入通常仅限于 C 末端区域。哺乳动物 TR1 和 E. crassus TR 之间的 3'-UTR 交换没有影响，因为这两种蛋白质都限制了 Sec 的插入。我们进一步发现，这些影响可以用硒蛋白特异性 SECIS 元件来解释。对其他硒蛋白中 Sec 插入的检查与该模型一致。这些数据表明，哺乳动物进化出了在硒蛋白内的天然位置限制 Sec 插入的能力，但以硒蛋白特异性的方式进行，并且该过程受 3'-UTR 中的 SECIS 元件控制。
