RNA binding protein FXR1-miR301a-3p axis contributes to p21WAF1 degradation in oral cancer.,PLOS Genetics

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RNA binding protein FXR1-miR301a-3p axis contributes to p21WAF1 degradation in oral cancer.
PLOS Genetics ( IF 4.0 ) Pub Date : 2020-01-15 , DOI: 10.1371/journal.pgen.1008580
Mrinmoyee Majumder ₁ , Viswanathan Palanisamy ₁

Affiliation

RNA-binding proteins (RBPs) associate with the primary, precursor, and mature microRNAs, which in turn control post-transcriptional gene regulation. Here, by small RNAseq, we show that RBP FXR1 controls the expression of a subset of mature miRNAs, including highly expressed miR301a-3p in oral cancer cells. We also confirm that FXR1 controls the stability of miR301a-3p. Exoribonuclease PNPT1 degrades miR301a-3p in the absence of FXR1 in oral cancer cells, and the degradation is rescued in the FXR1 and PNPT1 co-knockdown cells. In vitro, we show that PNPT1 is unable to bind and degrade the miRNA once the FXR1-miRNA complex forms. Both miR301a-3p and FXR1 cooperatively target the 3'-UTR of p21 mRNA to promote its degradation. Thus, our work illustrates the unique role of FXR1 that is critical for the stability of a subset of mature miRNAs or at least miR301a-3p to target p21 in oral cancer.

中文翻译：

RNA 结合蛋白 FXR1-miR301a-3p 轴有助于口腔癌中 p21WAF1 的降解。

RNA 结合蛋白 (RBP) 与初级、前体和成熟 microRNA 相关，进而控制转录后基因调控。在这里，通过小RNAseq，我们证明RBP FXR1控制成熟miRNA子集的表达，包括口腔癌细胞中高表达的miR301a-3p。我们还证实 FXR1 控制 miR301a-3p 的稳定性。在口腔癌细胞中缺乏 FXR1 的情况下，外切核糖核酸酶 PNPT1 会降解 miR301a-3p，并且这种降解在 FXR1 和 PNPT1 共敲低细胞中得以恢复。在体外，我们发现一旦 FXR1-miRNA 复合物形成，PNPT1 就无法结合并降解 miRNA。 miR301a-3p 和 FXR1 共同靶向 p21 mRNA 的 3'-UTR 以促进其降解。因此，我们的工作说明了 FXR1 的独特作用，它对于口腔癌中一部分成熟 miRNA 或至少 miR301a-3p 靶向 p21 的稳定性至关重要。

更新日期：2020-02-18

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