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Truncated initiation factor eIF4G lacking an eIF4E binding site can support capped mRNA translation
journal contribution
posted on 2023-06-08, 05:06 authored by Iraj K Ali, Linda McKendrick, Simon Morley, Richard J JacksonPicornavirus proteases cleave translation initiation factor eIF4G into a C-terminal two-thirds fragment (hereafter named p100) and an N-terminal one-third fragment, which interacts with the cap-binding factor eIF4E. As the timing of this cleavage correlates broadly with the shut-off of host cell protein synthesis in infected cells, a very widespread presumption has been that p100 cannot support capped mRNA translation. Through the use of an eIF4G-depleted reticulocyte lysate system, we show that this presumption is incorrect. Moreover, recombinant p100 can also reverse the inhibition of capped mRNA translation caused either by m7GpppG cap analogue, by 4E-BP1, which sequesters eIF4E and thus blocks its association with eIF4G, or by cleavage of endogenous eIF4G by picornavirus proteases. The concentration of p100 required for maximum translation of capped mRNAs is approx4-fold higher than the endogenous eIF4G concentration in reticulocyte lysates. Our results imply that picornavirus-induced shut-off is not due to an intrinsic inability of p100 to support capped mRNA translation, but to the viral RNA outcompeting host cell mRNA for the limiting concentration of p100.
History
Publication status
- Published
Journal
EMBO JournalISSN
0261-4189Publisher
Nature Publishing GroupExternal DOI
Issue
15Volume
20Page range
4233-4242Department affiliated with
- Biochemistry Publications
Notes
LMcK and SM provided all the purified proteins essential for this work. SM directed some of the research and actively collaborated in the interpretation of these data and the writing of the manuscript with Prof. R. Jackson.Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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