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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.

Author information

1
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, BCMM, New Haven, CT 06536, USA. joan.steitz@yale.edu

Abstract

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.

PMID:
19754429
DOI:
10.1042/BST0370931
[Indexed for MEDLINE]

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