Translational repression of a splice variant of cynomolgus macaque CXCL1L by its C-terminal sequence
Translational repression of a splice variant of cynomolgus macaque CXCL1L by its C-terminal sequence
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食蟹猴 CXCL1L 剪接变体的 C 端序列的翻译抑制
DOI：
10.1089/jir.2016.0085
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Osamu Yoshie
中科院分区：
文献类型：
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作者：
Hisayuki Nomiyama;Naoki Osada;Ichiro Takahashi;Keiji Terao;Kazuya Yamagata;Osamu Yoshie
我们之前从食蟹猴中分离出一个cDNA克隆，编码一种新的CXC趋化因子，我们将其命名为cxcl1l，因为它与cxcl1非常相似。然而，cDNA由3个外显子组成，而不是在其他CXC趋化因子中通常看到的4个外显子。在这里，我们分离了编码cxcl1l全长变体的cDNA，我们将其命名为cxcl1l β。cxcl1l β比原来的cxcl1l长50个氨基酸，我们现在称之为mcxcl1l α。xcl1l β mrna在食蟹猕猴组织中的表达量远高于ancxcl1l α mrna。然而，与cxcl1l α相比，转染细胞产生的cxcl1l β蛋白较少。当第4外显子的编码区与cxcl1的c端融合，甚至与非分泌蛋白萤火虫荧光素酶融合时，融合蛋白也几乎不产生，尽管mrna大量表达。多聚体分析表明，抑制主要发生在翻译水平。此外，我们证明了cxcl1l β的c -末端5氨基酸对翻译抑制至关重要。因此，本研究揭示了一种控制cxcl1l剪接变体产生的独特翻译调控。由于xcl1l基因仅在旧大陆猴中发挥作用，我们还讨论了在灵长类动物进化过程中这些猴子中活性xcl1l基因保存的可能原因。
We previously isolated a cDNA clone from cynomolgus macaque encoding a novel CXC chemokine that we termedCXCL1Lfrom its close similarity toCXCL1. However, the cDNA consisted of 3 exons instead of 4 exons that were typically seen in other CXC chemokines. Here, we isolated a cDNA encoding the full-length variant ofCXCL1Lthat we termedCXCL1Lβ.CXCL1Lβis 50 amino acids longer than the originalCXCL1L, which we now termCXCL1Lα. TheCXCL1LβmRNA is much more abundantly expressed in the cynomolgus macaque tissues thanCXCL1LαmRNA. However,CXCL1Lβprotein was poorly produced by transfected cells compared with that ofCXCL1Lα. When the coding region of the fourth exon was fused to the C-terminus ofCXCL1or even to a nonsecretory protein firefly luciferase, the fused proteins were also barely produced, although the mRNAs were abundantly expressed. The polysome profiling analysis suggested that the inhibition was mainly at the translational level. Furthermore, we demonstrated that the C-terminal 5 amino acids ofCXCL1Lβwere critical for the translational repression. The present study, thus, reveals a unique translational regulation controlling the production of a splicing variant ofCXCL1L. Since theCXCL1Lgene is functional only in the Old World monkeys, we also discuss possible reasons for the conservation of the activeCXCL1Lgene in these monkeys during the primate evolution.