Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay
Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay
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DOI：
10.1016/j.cell.2004.11.050
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发表时间：
2005-01-28
期刊：
影响因子：
64.5
通讯作者：
Maquat, LE
中科院分区：
文献类型：
--
作者：
Kim, YK;Furic, L;Maquat, LE
哺乳动物Staufen (Stau)1是一种RNA结合蛋白，被认为在mRNA转运和翻译控制中起作用。无义介导的mRNA衰变（NMD）降解在剪接产生的外显子-外显子连接上游终止翻译的异常和天然mRNA。在这里，我们描述了一种涉及Stau1、NMD因子Upf1和终止密码子的mRNA衰变机制。与NMD不同，该机制不涉及前mrna剪接，并在Upf2或Upf3X下调时发生。当Stau1被拴在终止密码子的下游时，它直接与Upf1结合并引发mRNA衰变。Stau1也与adp -核糖基化因子（Arf） 1mrna的3'-未翻译区相互作用。因此，下调Stau1或Upf1均可增加Arf1 mRNA的稳定性。这些发现表明Arf1 mRNA是stau1介导的衰变的天然靶点，数据表明其他mRNA也是天然靶点。我们讨论了这一途径作为细胞下调Stau1结合转录本表达的一种手段。
Mammalian Staufen (Stau)1 is an RNA binding protein that is thought to function in mRNA transport and translational control. Nonsense-mediated mRNA decay(NMD) degrades abnormal and natural mRNAs that terminate translation sufficiently upstream of a splicing-generated exon-exon junction. Here we describe an mRNA decay mechanism that involves Stau1, the NMD factor Upf1, and a termination codon. Unlike NMD, this mechanism does not involve pre-mRNA splicing and occurs when Upf2 or Upf3X is downregulated. Stau1 binds directly to Upf1 and elicits mRNA decay when tethered downstream of a termination codon. Stau1 also interacts with the 3'-untranslated region of ADP-ribosylation factor (Arf)1 mRNA. Accordingly, downregulating either Stau1 or Upf1 increases Arf1 mRNA stability. These findings suggest that Arf1 mRNA is a natural target for Stau1-mediated decay, and data indicate that other mRNAs are also natural targets. We discuss this pathway as a means for cells to downregulate the expression of Stau1 binding transcripts.