A potential role for initiator-tRNA in pre-mRNA splicing regulation
A potential role for initiator-tRNA in pre-mRNA splicing regulation
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DOI：
10.1073/pnas.0911561107
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发表时间：
2010-06-22
影响因子：
11.1
通讯作者：
Sperling, Joseph
中科院分区：
文献类型：
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作者：
Kamhi, Eyal;Raitskin, Oleg;Sperling, Joseph
翻译起始子-tRNA通过其反密码子三联体CAU和mRNA中的通用起始密码子AUG之间的特异性碱基配对，在原核和真核细胞中蛋白质合成的起始中起着至关重要的作用。在这里，我们表明，启动子-tRNA也可以采取行动，在某种程度上，是独立的蛋白质翻译中的作用，作为一个前mRNA剪接调节。具体而言，我们表明，选择性剪接事件，诱导的突变在翻译起始AUG密码子可以抑制表达启动子-tRNA结构携带反密码子突变，补偿AUG突变。这些突变的起始转运RNA似乎不带氨基酸。我们的研究结果意味着，识别的起始AUG序列的反密码子三联体的起始-tRNA在其卸载状态中发挥了作用，在质量控制剪接在细胞核中的一个尚未解决的机制。确定启动子-tRNA作为一个transacting剪接调节表明一种新的参与剪接调节，这种分子，并提供了一个关键的一步破译这一有趣的机制。
The translation initiator-tRNA plays a crucial role in the initiation of protein synthesis in both prokaryotic and eukaryotic cells, by employing specific base pairing between its anticodon triplet CAU and the general initiation codon AUG in the mRNA. Here we show that the initiator-tRNA may also act, in a manner that is independent of its role in protein translation, as a pre-mRNA splicing regulator. Specifically, we show that alternative splicing events that are induced by mutations in the translation initiation AUG codon can be suppressed by expressing initiator-tRNA constructs carrying anticodon mutations that compensate for the AUG mutations. These mutated initiator-tRNAs appeared to be uncharged with an amino acid. Our results imply that recognition of the initiation AUG sequence by the anticodon triplet of initiator-tRNA in its unloaded state plays a role in quality control of splicing in the cell nucleus by a yet unresolved mechanism. Identifying the initiator-tRNA as a transacting splicing regulator suggests a novel involvement of this molecule in splicing regulation and provides a critical step toward deciphering this intriguing mechanism.