Spliceostatin A stabilizes CDKN1B mRNA through the 3′ UTR
Spliceostatin A stabilizes CDKN1B mRNA through the 3′ UTR
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剪接抑素 A 通过 3 UTR 稳定 CDKN1B mRNA
DOI：
10.1016/j.bbrc.2022.03.085
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Daisuke Kaida and Kenta Shida
中科院分区：
文献类型：
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作者：
Tanaka Saki;Morita Mikio;Yamagishi Tatsuya;Madapally Hridya Valia;Hayashida Kenichi;Khandelia Himanshu;Gerle Christoph;Shigematsu Hideki;Oshima Atsunori;Abe Kazuhiro;杉本 宏;Daisuke Kaida and Kenta Shida
前体mRNA剪接是真核生物基因表达的重要机制之一，因此剪接抑制影响多种细胞功能。我们以前报道，强效剪接抑制剂spliceostatin A（SSA）导致细胞周期停滞在G1和G2/M期。由CDKN 1B基因编码的p27细胞周期蛋白依赖性激酶抑制剂的上调是SSA治疗引起G1期阻滞的原因之一。然而，SSA上调p27的分子机制仍不清楚。在本研究中，我们发现SSA处理引起p27蛋白的稳定和CDKN 1B mRNA的增加。SSA不影响CDKN 1B基因的转录，但稳定CDKN 1B mRNA的表达。最后，我们发现CDKN 1B mRNA的3′非翻译区参与了稳定化过程。这些结果表明，CDKN 1B mRNA的稳定是SSA上调p27蛋白的原因之一。
Pre-mRNA splicing is one of the most important mechanisms in gene expression in eukaryotes, and therefore splicing inhibition affects various cellular functions. We previously reported that the potent splicing inhibitor spliceostatin A (SSA) causes cell cycle arrest at G1 and G2/M phases. Upregulation of the p27 cyclin dependent kinase inhibitor, encoded by theCDKN1Bgene, is one of the reasons for G1 phase arrest caused by SSA treatment. However, the molecular mechanism of p27 upregulation by SSA remains unknown. In this study, we found that SSA treatment caused stabilization of the p27 protein and increase ofCDKN1BmRNA. SSA did not affect transcription ofCDKN1Bgene, but stabilizedCDKN1BmRNA. Finally, we revealed that the 3′ untranslated region ofCDKN1BmRNA was involved in the stabilization. These results suggest that stabilization ofCDKN1BmRNA is one of the reasons of upregulation of the p27 protein by SSA.