Separate cis-trans Pathways Post-transcriptionally Regulate Murine CD154 (CD40 Ligand) Expression: A NOVEL FUNCTION FOR CA REPEATS IN THE 3′-UNTRANSLATED REGION*
Hamilton, B. JoNell
Terry, Benjamin M.
Mouland, Andrew J.
Rigby, William C.
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CitationHamilton, B. JoNell, Xiao-Wei Wang, Jane Collins, Donald Bloch, Alan Bergeron, Brian Henry, Benjamin M. Terry, Moe Zan, Andrew J. Mouland, and William F. C. Rigby. 2008. “Separatecis-transPathways Post-Transcriptionally Regulate Murine CD154 (CD40 Ligand) Expression.” Journal of Biological Chemistry 283 (37). American Society for Biochemistry & Molecular Biology (ASBMB): 25606–16. doi:10.1074/jbc.m802492200.
AbstractWe report a role for CA repeats in the 3'-untranslated region (3'-UTR) in regulating CD154 expression. Human CD154 is encoded by an unstable mRNA; this instability is conferred in cis by a portion of its 3'-UTR that includes a polypyrimidine-rich region and CA dinucleotide repeat. We demonstrate similar instability activity with the murine CD154 3'-UTR. This instability element mapped solely to a conserved 100-base CU-rich region alone, which we call a CU-rich response element. Surprisingly, the CA dinucleotide-rich region also regulated reporter expression but at the level of translation. This activity was associated with poly(A) tail shortening and regulated by heterogeneous nuclear ribonucleoprotein L levels. We conclude that the CD154 3'-UTR contains dual cis-acting elements, one of which defines a novel function for exonic CA dinucleotide repeats. These findings suggest a mechanism for the association of 3'-UTR CA-rich response element polymorphisms with CD154 overexpression and the subsequent risk of autoimmune disease.
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