Unique translation initiation of mRNAs-containing TISU element

被引:83
作者
Elfakess, Rofa [1 ]
Sinvani, Hadar [1 ]
Haimov, Ora [1 ]
Svitkin, Yuri [2 ,3 ]
Sonenberg, Nahum [2 ,3 ]
Dikstein, Rivka [1 ]
机构
[1] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel
[2] McGill Univ, Dept Biochem, Montreal, PQ H3A 1A3, Canada
[3] McGill Univ, Goodman Canc Ctr, Montreal, PQ H3A 1A3, Canada
关键词
START CODON RECOGNITION; 40S RIBOSOMAL-SUBUNIT; SECONDARY STRUCTURE; EUKARYOTIC RIBOSOMES; PROTEIN DHX29; MECHANISMS; COMPLEXES; EIF1; SELECTION; POSITION;
D O I
10.1093/nar/gkr484
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:7598 / 7609
页数:12
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