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Recruitment and activation of mRNA decay ... s in the proteins TTP and BRF-1
Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1.
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In human cells, a critical pathway in gene regulation subjects mRNAs with AU-rich elements (AREs) to rapid decay by a poorly understood process. AREs have been shown to directly activate deadenylation, decapping, or 3'-to-5' exonucleolytic decay. We demonstrate that enzymes involved in all three of these mRNA decay processes, as well as 5'-to-3' exonucleolytic decay, associate with the protein tristetraprolin (TTP) and its homolog BRF-1, which bind AREs and activate mRNA decay. TTP and BRF-1 each contain two activation domains that can activate mRNA decay after fusion to a heterologous RNA-binding protein, and inhibit ARE-mediated mRNA decay when overexpressed. Both activation domains employ trans-acting factors to trigger mRNA decay, and the N-terminal activation domain functions as a binding platform for mRNA decay enzymes. Our data suggest that the TTP protein family functions as a molecular link between ARE-containing mRNAs and the mRNA decay machinery by recruitment of mRNA decay enzymes, and help explain how deadenylation, decapping, and exonucleolytic decay can all be independently activated on ARE-containing mRNAs. This describes a potentially regulated step in activation of mRNA decay.
Lykke-Andersen J, Wagner E
Genes & development
2005-02-01 00:00
19
3
351-61
Butyrate Response Factor 1,DNA-Binding Proteins,Endoribonucleases,Humans,Immediate-Early Proteins,Protein Structure, Tertiary,RNA, Messenger,Ribonucleases,TATA-Binding Protein Associated Factors,Tristetraprolin,BRF1 protein, human,Butyrate Response Factor 1,DNA-Binding Proteins,Immediate-Early Proteins,RNA, Messenger,TATA-Binding Protein Associated Factors,Tristetraprolin,ZFP36 protein, human,Endoribonucleases,Ribonucleases,DCP2 protein, human
Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA JensLykke-Anersencoloradoedu
Genes Dev.
NIGMS GM066811
0890-9369
10.1101/gad.1282305
19/3/351
817
True
15687258
