RNA-binding proteins (RBPs) form complexes with RNA, changing how the RNA is processed and thereby regulating gene expression. RBPs are important sources of gene regulation during organogenesis, including the development of the lungs. The RBP called Quaking (QK) is critical for embryogenesis, yet has not been studied in the developing lung. Here, we show that QK is widely expressed during rat lung development and into adulthood. The QK isoforms QK5 and QK7 co-localize to the nuclei of nearly all lung cells. QK6 is present in the nuclei and cytoplasm of mesenchymal cells and is only present in the epithelium during branching morphogenesis. QK knockdown in embryonic lung explants caused a greater number of multiciliated cells to appear in the airways, at the expense of basal cells. The mRNA of multiciliated cell genes and the abundance of FOXJ1/SOX2+ cells increased after knockdown, while P63/SOX2+ cells decreased. The cytokine IL-6, a known regulator of multiciliated cell differentiation, had increased mRNA levels after QK knockdown, although protein levels remained unchanged. Further studies are necessary to confirm whether QK acts as a blocker for the IL-6 induced differentiation of basal cell into multiciliated cells, and a conditional QK knockout would likely lead to additional discoveries on QK's role during lung development.

中文翻译：

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RNA结合蛋白Quaking调节发育中的肺中多纤毛和基底细胞的丰度

RNA结合蛋白（RBP）与RNA形成复合物，从而改变RNA的加工方式，从而调节基因表达。RBP是器官发生过程中基因调控的重要来源，包括肺部发育。称为Quaking（QK）的RBP对于胚胎发生至关重要，但尚未在发育中的肺中进行研究。在这里，我们表明QK在大鼠肺部发育和成年期广泛表达。QK同工型QK5和QK7共同定位在几乎所有肺细胞的细胞核中。QK6存在于间充质细胞的核和细胞质中，仅在分支形态发生期间存在于上皮中。胚胎肺外植体中的QK抑制导致大量多纤毛细胞出现在气道中，但以基底细胞为代价。敲除后，多纤毛细胞基因的mRNA和FOXJ1 / SOX2 +细胞的丰度增加，而P63 / SOX2 +细胞减少。细胞因子IL-6，一种已知的多纤毛细胞分化的调节剂，在QK敲低后具有增加的mRNA水平，尽管蛋白质水平保持不变。有必要进行进一步的研究以确认QK是否能作为IL-6诱导的基底细胞分化为多纤毛细胞分化的阻滞剂，而条件性QK敲除可能会导致QK在肺发育过程中的作用的其他发现。