ABSTRACT

Many long noncoding RNAs (lncRNAs) are localized in the nucleus and play important roles in various biological processes, including cell proliferation, differentiation and antiviral response. Yet, it remains unclear how some nuclear lncRNAs are turned over. Here we show that the heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) controls expression levels of NEAT1v2, a lncRNA involved in the formation of nuclear paraspeckles. hnRNPH1 associates, in an RNA-independent manner, with the RNA helicase MTR4/MTREX, an essential co-factor of the nuclear ribonucleolytic RNA exosome. hnRNPH1 localizes in nuclear speckles and depletion of hnRNPH1 enhances NEAT1v2-mediated expression of the IL8 mRNA, encoding a cytokine involved in the innate immune response. Taken together, our results indicate that the hnRNPH1-MTR4 linkage regulates IL8 expression through the degradation of NEAT1v2 RNA.

摘要

许多长链非编码 RNA (lncRNA) 位于细胞核中，在细胞增殖、分化和抗病毒反应等各种生物过程中发挥重要作用。然而，目前尚不清楚一些核 lncRNA 是如何被翻转的。在这里，我们显示异质核核糖核蛋白 H1 (hnRNPH1) 控制 NEAT1v2 的表达水平，NEAT1v2是一种参与核副啄木鸟形成的 lncRNA。hnRNPH1 以不依赖 RNA 的方式与 RNA 解旋酶 MTR4/MTREX 结合，后者是核糖核酸外泌体的重要辅助因子。hnRNPH1 定位于核斑点，hnRNPH1 的缺失增强了 NEAT1v2介导的IL8表达mRNA，编码参与先天免疫反应的细胞因子。总之，我们的结果表明 hnRNPH1-MTR4 连接通过NEAT1v 2 RNA的降解来调节IL8的表达。