Eukaryotic translation initiation factor 4G (eIF4G) coordinates interactions with eIF4A, eIF4B, and eIF4E in binding and translation of the barley yellow dwarf virus 3' cap-independent translation element (BTE)


Publication Type:

Journal Article


J. Biol. Chem., Volume 292, p.5921-5931 (2017)


<p>Barley yellow dwarf virus RNA, lacking a 5 cap and a 3<br />
poly(A) tail, contains a cap-independent translation element<br />
(BTE) in the 3-untranslated region that interacts with host<br />
translation initiation factor eIF4G. To determine how eIF4G<br />
recruits the mRNA, three eIF4G deletion mutants were constructed:<br />
(i) eIF4G601–1196, containing amino acids 601–1196,<br />
including the putative BTE-binding region, and binding<br />
domains for eIF4E, eIF4A, and eIF4B; (ii) eIF4G601–1488,<br />
which contains an additional C-terminal eIF4A-binding domain;<br />
and (iii) eIF4G742–1196, which lacks the eIF4E-binding<br />
site. eIF4G601–1196 binds BTE tightly and supports efficient<br />
translation. The helicase complex, consisting of eIF4A,<br />
eIF4B, and ATP, stimulated BTE binding with eIF4G601–1196<br />
but not eIF4G601–1488, suggesting that the eIF4A binding<br />
domains may serve a regulatory role, with the C-terminal binding<br />
site having negative effects. eIF4E binding to eIF4G601–<br />
1196 induced a conformational change, significantly increasing<br />
the binding affinity to BTE. A comparison of the binding of<br />
eIF4G deletion mutants with BTEs containing mutations<br />
showed a general correlation between binding affinity and ability<br />
to facilitate translation. In summary, these results reveal a<br />
new role for the helicase complex in 3 cap-independent translation<br />
element-mediated translation and show that the functional<br />
core domain of eIF4G plus an adjacent probable RNAbinding<br />
domain mediate translation initiation.</p>