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2015 ; 35
(22
): 3921-32
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Tristetraprolin Recruits Eukaryotic Initiation Factor 4E2 To Repress Translation
of AU-Rich Element-Containing mRNAs
#MMPMID26370510
Tao X
; Gao G
Mol Cell Biol
2015[Nov]; 35
(22
): 3921-32
PMID26370510
show ga
Tristetraprolin (TTP) regulates the expression of AU-rich element-containing
mRNAs through promoting the degradation and repressing the translation of target
mRNA. While the mechanism for promoting target mRNA degradation has been
extensively studied, the mechanism underlying translational repression is not
well established. Here, we show that TTP recruits eukaryotic initiation factor
4E2 (eIF4E2) to repress target mRNA translation. TTP interacted with eIF4E2 but
not with eIF4E. Overexpression of eIF4E2 enhanced TTP-mediated translational
repression, and downregulation of endogenous eIF4E2 or overexpression of a
truncation mutant of eIF4E2 impaired TTP-mediated translational repression.
Overexpression of an eIF4E2 mutant that lost the cap-binding activity also
impaired TTP's activity, suggesting that the cap-binding activity of eIF4E2 is
important in TTP-mediated translational repression. We further show that TTP
promoted eIF4E2 binding to target mRNA. These results imply that TTP recruits
eIF4E2 to compete with eIF4E to repress the translation of target mRNA. This
notion is supported by the finding that downregulation of endogenous eIF4E2
increased the production of tumor necrosis factor alpha (TNF-?) protein without
affecting the mRNA levels in THP-1 cells. Collectively, these results uncover a
novel mechanism by which TTP represses target mRNA translation.