Separate cis-trans pathways post-transcriptionally regulate murine CD154 (CD40 ligand) expression -: A novel function for CA repeats in the 3′-untranslated region
Separate cis-trans pathways post-transcriptionally regulate murine CD154 (CD40 ligand) expression -: A novel function for CA repeats in the 3′-untranslated region
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DOI：
10.1074/jbc.m802492200
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发表时间：
2008-09-12
影响因子：
4.8
通讯作者：
Rigby, William F. C.
中科院分区：
文献类型：
--
作者：
Hamilton, B. JoNell;Wang, Xiao-Wei;Rigby, William F. C.
我们报道了3'-非翻译区（3'-UTR）中的CA重复序列在调节CD154表达中的作用。人类CD154是由一个不稳定的mRNA编码的；这种不稳定性是由其3'-UTR的一部分顺式赋予的，其中包括一个富含多嘧啶的区域和CA二核苷酸重复。我们在小鼠CD154 3'-UTR中证明了类似的不稳定性活性。这种不稳定元件仅映射到一个保守的100碱基富cu区域，我们称之为富cu响应元件。令人惊讶的是，CA富含二核苷酸的区域也调节了报告基因的表达，但只是在翻译水平上。这种活性与poly(A)尾巴缩短有关，并受异质核糖-核蛋白L水平的调控。我们得出结论，CD154 3'-UTR包含两个顺式作用元件，其中一个定义了外显子CA二核苷酸重复的新功能。这些发现提示了3'-UTR富含ca的反应元件多态性与CD154过表达和随后的自身免疫性疾病风险相关的机制。
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.