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Translational Repression and elF4A2 Activity Are Critical for MicroRNA-Mediated Gene Regulation.

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Title: Translational Repression and elF4A2 Activity Are Critical for MicroRNA-Mediated Gene Regulation.
Authors: 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.
Source: Science (pre-March 2025). 4/5/2013, Vol. 340 Issue 6128, p82-85. 4p.
Subjects: MicroRNA genetics, Genetic regulation, RNA helicase genetics, Genetic translation, Linear statistical models, Molecular biology, Messenger RNA
Abstract: 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. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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PubType: Academic Journal
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  Data: Translational Repression and elF4A2 Activity Are Critical for MicroRNA-Mediated Gene Regulation.
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  Data: <searchLink fieldCode="AR" term="%22Meijer%2C+H%2E+A%2E%22">Meijer, H. A.</searchLink><br /><searchLink fieldCode="AR" term="%22Kong%2C+Y%2E+W%2E%22">Kong, Y. W.</searchLink><br /><searchLink fieldCode="AR" term="%22Lu%2C+W%2E+T%2E%22">Lu, W. T.</searchLink><br /><searchLink fieldCode="AR" term="%22Wilczynska%2C+A%2E%22">Wilczynska, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Spriggs%2C+R%2E+V%2E%22">Spriggs, R. V.</searchLink><br /><searchLink fieldCode="AR" term="%22Robinson%2C+S%2E+W%2E%22">Robinson, S. W.</searchLink><br /><searchLink fieldCode="AR" term="%22Godfrey%2C+J%2E+D%2E%22">Godfrey, J. D.</searchLink><br /><searchLink fieldCode="AR" term="%22Willis%2C+A%2E+E%2E%22">Willis, A. E.</searchLink><br /><searchLink fieldCode="AR" term="%22Bushell%2C+M%2E%22">Bushell, M.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 4/5/2013, Vol. 340 Issue 6128, p82-85. 4p.
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  Data: <searchLink fieldCode="DE" term="%22MicroRNA+genetics%22">MicroRNA genetics</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+regulation%22">Genetic regulation</searchLink><br /><searchLink fieldCode="DE" term="%22RNA+helicase+genetics%22">RNA helicase genetics</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+translation%22">Genetic translation</searchLink><br /><searchLink fieldCode="DE" term="%22Linear+statistical+models%22">Linear statistical models</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+biology%22">Molecular biology</searchLink><br /><searchLink fieldCode="DE" term="%22Messenger+RNA%22">Messenger RNA</searchLink>
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – SubjectFull: MicroRNA genetics
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      – SubjectFull: RNA helicase genetics
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      – SubjectFull: Genetic translation
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      – SubjectFull: Molecular biology
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      – SubjectFull: Messenger RNA
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              Text: 4/5/2013
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