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: |
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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 |
Externí odkaz: |
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