Misfolded human tRNA isodecoder binds and neutralizes a 3′ UTR-embedded Alu element

Misfolded human tRNA isodecoder binds and neutralizes a 3′ UTR-embedded Alu element
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DOI:
10.1073/pnas.1103698108
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发表时间:
2011-10-04
影响因子:
11.1
通讯作者:
Frugier, Magali
Frugier, Magali
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Rudinger-Thirion, Joelle;Lescure, Alain;Frugier, Magali

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几类小的非编码RNA在细胞代谢中起着关键作用,包括mRNA解码、RNA加工和mRNA稳定性。本研究表明,与人类trna衍生序列相对应的tRNAAsp同位解码器与人类天门冬氨酸- trna合成酶mRNA的3' UTR中嵌入的Alu RNA元件结合。tRNA和Alu RNA这两类众所周知的RNA分子之间的相互作用是由一个意想不到的结构基序驱动的,并诱导了3' UTR的全局重排。此外,这个3' UTR包含两个功能性聚腺苷化信号。我们提出了一个模型,其中tRNA/Alu相互作用将调节两个备选聚腺苷化位点的可及性并调节mRNA的稳定性。这种独特的调控机制将基因表达与RNA聚合酶III转录联系起来,并可能在灵长类动物特异性信号通路中发挥作用。
Several classes of small noncoding RNAs are key players in cellular metabolism including mRNA decoding, RNA processing, and mRNA stability. Here we show that a tRNAAsp isodecoder, corresponding to a human tRNA-derived sequence, binds to an embedded Alu RNA element contained in the 3' UTR of the human aspartyl-tRNA synthetase mRNA. This interaction between two well-known classes of RNA molecules, tRNA and Alu RNA, is driven by an unexpected structural motif and induces a global rearrangement of the 3' UTR. Besides, this 3' UTR contains two functional polyadenylation signals. We propose a model where the tRNA/Alu interaction would modulate the accessibility of the two alternative polyadenylation sites and regulate the stability of the mRNA. This unique regulation mechanism would link gene expression to RNA polymerase III transcription and may have implications in a primate-specific signal pathway.