MicroRNAs interfere with the initiation step of translation by inhibiting the function of the 5' cap structure and 3' poly(A) tail, implicating eukaryotic initiation factor 4E as a molecular target.
MicroRNAs repress translation by interfering with the initiation step, specifically targeting the function of the 5' cap structure, poly(A) tail, and eIF4E.
Effect estimate: 5.5-fold repression
MicroRNAs (miRNAs) repress translation of target mRNAs by interaction with partially mismatched sequences in their 3' UTR. The mechanism by which they act on translation has remained largely obscure. We examined the translation of mRNAs containing four partially mismatched miRNA-binding sites in the 3' UTR in HeLa cells cotransfected with a cognate miRNA. The mRNAs were prepared by in vitro transcription and were engineered to employ different modes of translation initiation. We find that the 5' cap structure and the 3' poly(A) tail are each necessary but not sufficient for full miRNA-mediated repression of mRNA translation. Replacing the cap structure with an internal ribosome entry site from either the cricket paralysis virus or the encephalomyocarditis virus impairs miRNA-mediated repression. Collectively, these results demonstrate that miRNAs interfere with the initiation step of translation and implicate the cap-binding protein eukaryotic initiation factor 4E as a molecular target.
Humphreys et al. (Tue,) conducted a other in Translation initiation mechanism. CXCR4 miRNA vs. let-7 miRNA or no miRNA was evaluated on Repression of mRNA translation (5.5-fold repression). MicroRNAs interfere with the initiation step of translation by inhibiting the function of the 5' cap structure and 3' poly(A) tail, implicating eukaryotic initiation factor 4E as a molecular target.