TNFα (tumour necrosis factor α) 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 TNFα and other cytokines. We found that the TNFα 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/G2-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.
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Discussion| September 21 2009
miRNPs: versatile regulators of gene expression in vertebrate cells1
Joan A. Steitz;
Joan A. Steitz 2
1Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, BCMM, New Haven, CT 06536, U.S.A.
2To whom correspondence should be addressed (email email@example.com).
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Publisher: Portland Press Ltd
Received: June 09 2009
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2009 Biochemical Society
Joan A. Steitz, Shobha Vasudevan; miRNPs: versatile regulators of gene expression in vertebrate cells. Biochem Soc Trans 1 October 2009; 37 (5): 931–935. doi: https://doi.org/10.1042/BST0370931
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