The Apaf-1 internal ribosome entry segment attains the correct structural conformation for function via interactions with PTB and unr

被引:212
作者
Mitchell, SA
Spriggs, KA
Coldwell, MJ
Jackson, RJ
Willis, AE
机构
[1] Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England
[2] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
D O I
10.1016/S1097-2765(03)00093-5
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
We have shown previously that polypyrimidine tract binding protein 1 (PTB) binds and activates the Apaf-1 internal ribosome entry segment (IRES) when the protein upstream of N-ras (unr) is prebound. Here we show that the Apaf-1 IRES is highly active in neuronal-derived cell lines due to the presence of the neuronal-enhanced version of PTB, nPTB. The unr and PTB/ nPTB binding sites have been located on the Apaf-1 IRES RNA, and a structural model for the IRES bound to these proteins has been derived. The ribosome landing site has been located to a single-stranded region, and this is generated by the binding of the nPTB and unr to the RNA. These data suggest that unr and nPTB act as RNA chaperones by changing the structure of the IRES into one that permits translation initiation.
引用
收藏
页码:757 / 771
页数:15
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