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Novel DNA-binding properties of the RNA-binding protein TIAR

By Esther A. Suswam, Yan Yan Li, Harry Mahtani and Peter H. King


TIA-1 related protein binds avidly to uridine-rich elements in mRNA and pre-mRNAs of a wide range of genes, including interleukin (IL)-8 and vascular endothelial growth factor (VEGF). The protein has diverse regulatory roles, which in part depend on the locus of binding within the transcript, including translational control, splicing and apoptosis. Here, we observed selective and potent inhibition of TIAR–RNP complex formation with IL-8 and VEGF 30-untrans lated regions (30-UTRs) using thymidine-rich deoxyoligonucleotide (ODN) sequences derived from the VEFG 30-UTR. We show by ultraviolet crosslinking and electrophoretic mobility shift assays that TIAR can bind directly to single-stranded, thymidine-rich ODNs but not to double-stranded ODNs containing the same sequence. TIAR had a nearly 6-fold greater affinity for DNA than RNA (K dapp 1:6 3 10 9 M versus 9:4 3 10 9 M). Truncation of TIAR indicated that the high affinity DNA-binding site overlaps with the RNA-binding site involving RNA recognition motif 2 (RRM2). However, RRM1 alone could also bind to DNA. Finally, we show that TIAR can be displaced from single-stranded DNA by active transcription through the binding site. These results provide a potential mechanism by which TIAR can shuttle between RNA and DNA ligands

Year: 2005
OAI identifier: oai:CiteSeerX.psu:
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