The role of the Drosophila TIS11 protein in the regulati

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The levels of mRNA in cells reflect a balance between rates of gene transcription and mRNA turnover. Although attention has focused on the control of transcription in the regulation of gene expression, the rates of mRNA turnover can be just as important in determining final mRNA concentrations. Rather than a single default pathway of mRNA decay, rates of mRNA turnover can differ dramatically among different mRNA species in a given cell type, between the same mRNA species in different cells, and with the same mRNA species and cell type when cells are exposed to distinct environmental stimuli. Turnover rate of some mRNAs can be influenced by cis-acting sequences, often within the 3'UTR. One of the best-studied examples is the AU-rich element (ARE). The mammalian tristetraprolin (TTP) protein can bind to AREs in the mRNAs encoding tumor necrosis factor alpha and granulocyte-macrophage colony stimulating factor and lead to their destabilization, through a process that may involve the removal of the poly(A) tail, or deadenylation. There are three other mammalian members of the TTP protein family. All of these proteins can act in the same way as TTP in cell transfection and cell-free assay systems to promote the deadenylation and instability of mRNA targets that contain AREs. Although recent knockout studies have identified potential roles for these proteins in widely disparate physiological processes, their target mRNAs are as yet unknown. In order to fully understand the molecular nature of how TTP and its family members act to promote mRNA deadenylation and destruction, it would be desirable to conduct studies in a simpler, genetically tractable organism in which only one member of this protein family is expressed. Drosophila melanogaster meets these criteria, expressing only a single member of this protein family (TIS11). The Drosophila Tis11 gene, however, may be differentially spliced to produce two different proteins. Essentially nothing is known about the function of this protein in Drosophila, although its transcript is expressed in the early embryo and in the adult.