Separate cis-trans Pathways Post-transcriptionally Regulate Murine CD154 (CD40 Ligand) Expression

Autor: William F. C. Rigby, Benjamin M. Terry, Brian L. Henry, Xiao Wei Wang, Moe Zan, Jane E. Collins, Daniel Bloch, B. JoNell Hamilton, Alan Bergeron, Andrew J. Mouland
Rok vydání: 2008
Předmět:
Zdroj: Journal of Biological Chemistry. 283:25606-25616
ISSN: 0021-9258
DOI: 10.1074/jbc.m802492200
Popis: We 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.
Databáze: OpenAIRE