Stability of RNA quadruplex in open reading frame determines proteolysis of human estrogen receptor α.

Stability of RNA quadruplex in open reading frame determines proteolysis of human estrogen receptor α.
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DOI:
10.1093/nar/gkt286
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发表时间:
2013-07
影响因子:
14.9
通讯作者:
Sugimoto N
Sugimoto N
中科院分区:
生物学2区
文献类型:
--
作者:
Endoh T;Kawasaki Y;Sugimoto N

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mRNA不仅编码决定氨基酸序列的信息,还编码调节翻译过程的额外信息层。值得注意的是,由稀有密码子或稳定的RNA结构引起的特定位置的翻译停止是调节蛋白质表达和结构的潜在因素之一。本研究揭示了人雌激素受体α(hERα)mRNA开放阅读框中的一个四链体形成潜能(quadruple-forming potential,QFP)序列在体外可形成平行的G-四链体并阻止翻译延伸。此外,当全长hERα和在QFP序列中含有同义突变的变体在细胞中表达时,观察到在特定位点切割的翻译产物,其数量取决于G-四链体的热力学稳定性。这些结果表明,在hERα mRNA编码区的G-四链体的形成影响hERα蛋白的折叠和蛋白水解,通过减缓或暂时停止翻译延伸。
mRNAs encodes not only information that determines amino acid sequences but also additional layers of information that regulate the translational processes. Notably, translational halt at specific position caused by rare codons or stable RNA structures is one of the potential factors regulating the protein expressions and structures. In this study, a quadruplex-forming potential (QFP) sequence derived from an open reading frame of human estrogen receptor α (hERα) mRNA was revealed to form parallel G-quadruplex and halt the translation elongation in vitro. Moreover, when the full-length hERα and variants containing synonymous mutations in the QFP sequence were expressed in cells, translation products cleaved at specific site were observed in quantities dependent on the thermodynamic stability of the G-quadruplexes. These results suggest that the G-quadruplex formation in the coding region of the hERα mRNA impacts folding and proteolysis of hERα protein by slowing down or temporarily stalling the translation elongation.
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