Separate cis-trans pathways post-transcriptionally regulate murine CD154 (CD40 ligand) expression -: A novel function for CA repeats in the 3′-untranslated region

被引：20

作者：

Hamilton, B. JoNell ^{[1
,2
]}

Wang, Xiao-Wei ^{[1
,2
]}

Collins, Jane ^{[1
,2
]}

Bloch, Donald ^{[3
,4
]}

Bergeron, Alan

Henry, Brian ^{[1
,2
]}

Terry, Benjamin M. ^{[5
]}

Zan, Moe ^{[1
,2
]}

Mouland, Andrew J. ^{[6
,7
]}

Rigby, William F. C. ^{[1
,2
]}

机构：

[1] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Lebanon, NH 03756 USA

[2] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Microbiol & Immunol, Lebanon, NH 03756 USA

[3] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Boston, MA 02114 USA

[5] New York Med Coll, Valhalla, NY 10595 USA

[6] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada

[7] McGill Univ, Montreal, PQ H3T 1E2, Canada

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 37期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1074/jbc.M802492200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：25606 / 25616

页数：11

共 51 条

[1] RNA granules [J].