lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3' UTRs via Alu elements.
lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3' UTRs via Alu elements.
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DOI：
10.1038/nature09701
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发表时间：
2011-02-10
期刊：
影响因子：
64.8
通讯作者：
Maquat, Lynne E.
中科院分区：
文献类型：
--
作者：
Gong, Chenguang;Maquat, Lynne E.
Staufen 1（STAU 1）介导的mRNA衰变（SMD）降解在其3 '-非翻译区（3' UTR）内结合双链（ds）RNA结合蛋白STAU 1的降解活性mRNA。早期的研究将ADP核糖基化因子1（ARF 1）mRNA中的STAU 1结合位点（SBS）定义为具有100个核苷酸顶点的19个碱基对茎。然而，我们无法在其他SMD靶标的3 'UTR内鉴定出可比较的结构。在这里，我们报告说，SBS可以通过SMD靶的3 'UTR内的Alu元件与细胞质和多腺苷酸化的长非编码RNA（lncRNA）内的另一Alu元件之间的不完全碱基配对形成。单个lncRNA可以下调SMD靶标的子集，并且不同的lncRNA可以下调相同的SMD靶标。这些是ncRNA和Alu元件以前未被认识到的功能。并非所有含有3 'UTR Alu元件的mRNA都靶向SMD，尽管存在靶向SMD的其它mRNA的互补lncRNA。大多数已知的反式作用RNA效应子由少于200个核苷酸组成，包括snoRNA和microRNA。我们发现STAU 1与mRNA的结合可以被lncRNA反式激活，这揭示了细胞将蛋白质募集到mRNA并介导其衰变的一种意想不到的策略。我们将这些lncRNA命名为“半（1/2）-sbsRNA”。
Staufen1 (STAU1)-mediated mRNA decay (SMD) degrades translationally active mRNAs that bind the double-stranded (ds)RNA binding protein STAU1 within their 3'-untranslated regions (3'UTRs). Earlier studies defined the STAU1 binding site (SBS) within ADP ribosylation factor 1 (ARF1) mRNA as a 19-base-pair stem with a 100-nucleotide apex. However, we were unable to identify comparable structures within the 3'UTRs of other SMD targets. Here we report that SBSs can be formed by imperfect base-pairing between an Alu element within the 3'UTR of an SMD target and another Alu element within a cytoplasmic and polyadenylated long noncoding RNA (lncRNA). Individual lncRNAs can downregulate a subset of SMD targets, and distinct lncRNAs can downregulate the same SMD target. These are previously unappreciated functions for ncRNAs and Alu elements. Not all mRNAs that contain a 3'UTR Alu element are targeted for SMD despite the presence of a complementary lncRNA that targets other mRNAs for SMD. Most known trans-acting RNA effectors consist of fewer than 200 nucleotides and include snoRNAs and microRNAs. Our finding that STAU1 binding to mRNAs can be transactivated by lncRNAs uncovers an unexpected strategy used by cells to recruit proteins to mRNAs and mediate their decay. We name these lncRNAs “half(½)-sbsRNAs”.
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