글번호
5583372
일 자
16.07.18
조회수
77
글쓴이
김은아
제목 : 2016-07-15 Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor.(권준영)
2016 Jun 15;534(7608):558-61. doi: 10.1038/nature17978.

Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor.


Abstract

Rocaglamide A (RocA) typifies a class of protein synthesis inhibitors that selectively kill aneuploid tumour cells and repress translation of specific messenger RNAs. RocA targets eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase; its messenger RNA selectivity is proposed to reflect highly structured 5' untranslated regions that depend strongly on eIF4A-mediated unwinding. However, rocaglate treatment may not phenocopy the loss of eIF4A activity, as these drugs actually increase the affinity between eIF4A and RNA. Here we show that secondary structure in 5' untranslated regions is only a minor determinant for RocA selectivity and that RocA does not repress translation by reducing eIF4A availability. Rather, in vitro and in cells, RocA specifically clamps eIF4A onto polypurine sequences in an ATP-independent manner. This artificially clamped eIF4A blocks 43S scanning, leading to premature, upstream translation initiation and reducing protein expression from transcripts bearing the RocA-eIF4A target sequence. In elucidating the mechanism of selective translation repression by this lead anti-cancer compound, we provide an example of a drug stabilizing sequence-selective RNA-protein interactions.

PMID:27309803
PMCID:PMC4946961 [Available on 2016-12-15]
DOI:10.1038/nature17978
첨부파일 첨부파일:
첨부파일이 없습니다.
목록으로
다음글 2016-07-22 Translation from the 5' untranslated region shapes the integrated stress response. (홍가영)
이전글 2016-07-08 ABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production.(Rahman MD Shafiq)