Details

Autor(en) / Beteiligte

• Meijer, H. A.
• Kong, Y. W.
• Lu, W. T.
• Wilczynska, A.
• Spriggs, R. V.
• Robinson, S. W.
• Godfrey, J. D.
• Willis, A. E.
• Bushell, M.

Titel

Translational Repression and eIF4A2 Activity Are Critical for MicroRNA-Mediated Gene Regulation

Ist Teil von

• Science (American Association for the Advancement of Science), 2013-04, Vol.340 (6128), p.82-85

Ort / Verlag

United States: American Association for the Advancement of Science

Erscheinungsjahr

2013

Quelle

Science Online_科学在线

Beschreibungen/Notizen

• MicroRNAs (miRNAs) control gene expression through both translational repression and degradation of target messenger RNAs (mRNAs). However, the interplay between these processes and the precise molecular mechanisms involved remain unclear. Here, we show that translational inhibition is the primary event required for mRNA degradation. Translational inhibition depends on miRNAs impairing the function of the elF4F initiation complex. We define the RNA helicase elF4A2 as the key factor of elF4F through which miRNAs function. We uncover a correlation between the presence of miRNA target sites in the 3’ untranslated region (3’UTR) of mRNAs and secondary structure in the 5’UTR and show that mRNAs with unstructured 5’UTRs are refractory to miRNA repression. These data support a linear model for miRNA-mediated gene regulation in which translational repression via elF4A2 is required first, followed by mRNA destabilization.