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Mol Cell Biochem. 2005 Apr;272(1-2):107-18.

Regulation of urokinase receptor mRNA stability by hnRNP C in lung epithelial cells.

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Department of Specialty Care Services, The University of Texas Health Center at Tyler, Tyler, TX 75708, USA.


Increased urokinase receptor (uPAR) expression as well as stabilisation of uPAR mRNA contribute to the pathogenesis of lung inflammation and neoplasia. Post-transcriptional regulation of uPAR mRNA involves interaction of both coding and 3'-UTR sequences with regulatory uPAR mRNA binding proteins (Bps). In order to identify novel regulatory interactions, we performed gel mobility shift and UV cross-linking assays and found two distinct uPAR mRNA-protein complexes. We identified a rapidly migrating 40 kDa uPAR mRNABp that selectively bound a 110 nucleotide (nt) fragment of the uPAR mRNA 3'UTR. Chimeric beta-globin/uPAR mRNA containing the 110 nt 40 kDa protein binding fragment destabilised stable beta-globin mRNA with a rate of decay identical to that of chimeric beta-globin/uPAR containing the full uPAR 3'UTR. The 40 kDa uPAR 3'UTR Bp was purified using poly (U) sepharose and identified as heterogeneous nuclear ribonucleoprotein C (hnRNPC). Finally, we confirmed its interaction with the uPAR mRNA 3' UTR by gel mobility supershift assay using an anti-hnRNPC antibody. Direct in vivo interaction of hnRNPC with the uPAR mRNA 3'UTR was demonstrated by immunoprecipitation and combined RT PCR-Southern blotting assay. Co-transfection of hnRNPC cDNA in Beas2B cells reversed destabilisation of chimeric beta-globin/uPAR 3'UTR mRNA and its over-expression also induced uPAR protein and mRNA expression through stabilisation of uPAR mRNA. These observations indicate a novel mechanism of uPAR gene regulation in lung epithelial cells in which cis elements within a 110 nt uPAR mRNA 3'UTR sequence interact with hnRNPC to regulate uPAR mRNA stability.

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