Unique translation initiation of mRNAs-containing TISU element
Unique translation initiation of mRNAs-containing TISU element
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DOI：
10.1093/nar/gkr484
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发表时间：
2011-09-01
影响因子：
14.9
通讯作者：
Dikstein, Rivka
中科院分区：
文献类型：
--
作者：
Elfakess, Rofa;Sinvani, Hadar;Dikstein, Rivka
简短5'UTR（TISU）的翻译启动器是转录和翻译启动的独特调节元素。它存在于具有基本细胞功能和非常短的未翻译区域（5'UTR）的大量基因中。在这里，我们调查了在各种情况下与AUG的简短5'UTR mRNA的翻译启动。将5'UTR的长度降低到最小功能大小会增加弱和强的启动器的泄漏扫描，但几乎不会影响TISU指导的翻译起始和核糖体结合。与Tisu mRNA的核糖体相互作用是帽依赖性的，并且涉及AUM下游核苷酸，以补偿缺乏5'UTR接触的情况。有趣的是，EIF1在弱或强的情况下抑制了封闭式的AUM选择，但在TISU中不抑制。此外，TISU定向的翻译不受RNA解旋酶EIF4A的抑制影响。因此，TISU无需扫描就可以指导有效的CAP依赖性翻译起始，而当EIF1和EIF4A的细胞内水平波动时，这种机制将是有利的。
Translation Initiator of Short 5' UTR (TISU) is a unique regulatory element of both transcription and translation initiation. It is present in a sizable number of genes with basic cellular functions and a very short untranslated region (5' UTR). Here, we investigated translation initiation from short 5' UTR mRNAs with AUG in various contexts. Reducing 5' UTR length to the minimal functional size increases leaky scanning from weak and strong initiators but hardly affects translation initiation and ribosomal binding directed by TISU. Ribosome interaction with TISU mRNA is cap dependent and involves AUG downstream nucleotides that compensate for the absent 5' UTR contacts. Interestingly, eIF1 inhibits cap-proximal AUG selection within weak or strong contexts but not within TISU. Furthermore, TISU-directed translation is unaffected by inhibition of the RNA helicase eIF4A. Thus, TISU directs efficient cap-dependent translation initiation without scanning, a mechanism that would be advantageous when intracellular levels of eIF1 and eIF4A fluctuate.