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Biochem Soc Trans. 2009 Oct;37(Pt 5):931-5. doi: 10.1042/BST0370931.

miRNPs: versatile regulators of gene expression in vertebrate cells.

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Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, BCMM, New Haven, CT 06536, USA.


TNFalpha (tumour necrosis factor alpha) mRNA bears in its 3'-UTR (untranslated region) a conserved ARE (AU-rich element), a signal that exerts tight post-transcriptional control over the expression of TNFalpha and other cytokines. We found that the TNFalpha ARE increases translational efficiency when cell growth is arrested, a physiologically relevant state occurring during inflammation, angiogenesis and monocyte differentiation. Under these conditions, called quiescence, the miRNP (microribonucleoprotein)-associated proteins FXR1 (Fragile X mental retardation-related protein 1) and AGO2 (Argonaute 2), which are usually considered negative regulators, are transformed into effector molecules that bind the ARE to activate translation. We then identified a specific miRNA (microRNA) that directs the association of AGO2 and FXR1 with the ARE during translational up-regulation. Two other well-characterized miRNAs likewise promote translation activation in quiescent or in contact-inhibited cells; yet, they repress translation in proliferating cells in the late S/G(2)-phase. We conclude that translational regulation by miRNPs oscillates between repression and activation as a function of the cell cycle. The activating role of miRNAs is now being confirmed in the immature Xenopus oocyte, which mimics the quiescent state.

[Indexed for MEDLINE]

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