Upstream open reading frames regulate the expression of the nuclear Wnt13 isoforms.
Upstream open reading frames regulate the expression of the nuclear Wnt13 isoforms.
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上游开放阅读框调节核 Wnt13 亚型的表达。
DOI：
10.1016/j.bbrc.2007.12.092
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发表时间：
2008
影响因子：
3.1
通讯作者：
Mao,CatherineD
中科院分区：
文献类型：
--
作者：
Tang,Tao;Rector,Kyle;Barnett,CoreyD;Mao,CatherineD
Wnt蛋白在发育过程中控制细胞存活和细胞命运。虽然Wnt的表达在时空上受到严格的调控，但其在转录和翻译水平上的机制还不清楚。我们已经在Wnt 13 B和Wnt 13 C mRNA中鉴定了下游翻译起始密码子AUG（+74），其负责Wnt 13核形式的表达。在这份报告中，我们证明了核Wnt 13 C形式的表达是响应于应激和细胞凋亡而进行调节的。尽管Wnt 13 C和Wnt 13 B mRNA的5′-前导序列对翻译具有抑制作用，但它们没有显示出内部核糖体进入位点活性，如双顺反子报告基因测定所证明的。然而，上游AUG（-99）和AUG（+1）起始密码子的突变或缺失消除了这些翻译抑制作用，表明Wnt 13 C表达受上游开放阅读框控制。由于长的5′-非翻译区和短的上游开放阅读框是其他Wnt转录物的特征，我们目前关于Wnt 13表达的翻译控制的数据为进一步研究Wnt表达的翻译控制作为其亚细胞定位和活性的调节剂开辟了道路。
Wnt proteins control cell survival and cell fate during development. Although Wnt expression is tightly regulated in a spatio-temporal manner, the mechanisms involved both at the transcriptional and translational levels are poorly defined. We have identified a downstream translation initiation codon, AUG(+74), in Wnt13B and Wnt13C mRNAs responsible for the expression of Wnt13 nuclear forms. In this report, we demonstrate that the expression of the nuclear Wnt13C form is translationally regulated in response to stress and apoptosis. Though the 5′-leaders of both Wnt13C and Wnt13B mRNAs have an inhibitory effect on translation, they did not display an internal ribosome entry site activity as demonstrated by dicistronic reporter assays. However, mutations or deletions of the upstream AUG(−99) and AUG(+1) initiation codons abrogate these translation inhibitory effects, demonstrating that Wnt13C expression is controlled by upstream open reading frames. Since long 5′-untranslated region with short upstream open reading frames characterize other Wnt transcripts, our present data on the translational control of Wnt13 expression open the way to further studies on the translation control of Wnt expression as a modulator of their subcellular localization and activity.