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Regulating the activity of microRNPs in vertebrate cells
Author(s) -
Steitz Joan A.,
Vasudevan Shobha,
Cazalla Demian
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.90.3
Subject(s) - microbiology and biotechnology , translation (biology) , microrna , biology , psychological repression , effector , translational regulation , downregulation and upregulation , tumor necrosis factor alpha , xenopus , messenger rna , genetics , gene expression , immunology , gene
Tumor necrosis factor alpha (TNFalpha) mRNA bears in its 3' UTR a conserved AU‐rich sequence (ARE), a signal that exerts tight post‐transcriptional control over the expression of TNFalpha and other cytokines. We have discovered that the TNFalpha ARE increases translational efficiency when cell growth is arrested, a physiologically relevant state occurring during inflammation, angiogenesis and monocyte differentiation. Surprisingly, under these conditions, called quiescence, the microRNP‐associated proteins FXR1 and AGO2, which are usually considered negative regulators, are transformed into effector molecules that bind the ARE to activate translation. We then identified a specific microRNA that directs the association of AGO2 and FXR1 with the ARE during translation upregulation. Two other well‐characterized microRNAs likewise promote translation activation in quiescent or in contact‐inhibited cells; yet, they repress translation in proliferating cells late in S phase. We suggest that translation regulation by microRNPs oscillates between repression and activation as a function of the cell cycle. We are currently confirming the activating role of microRNAs in a naturally quiescent cell, the Xenopus oocyte. We are also investigating the mechanism by which H. saimiri, a primate gamma herpesvirus, regulates microRNA function in latently transformed T cells.