microRNAs (miRNAs) and RNA binding proteins (RBPs) regulate gene expression at the post-transcriptional level, but the extent to which these key regulators of gene expression coordinate and the precise mechanisms of their coordination are not well understood. RNA binding proteins often have recognizable RNA binding domains that correlate with specific protein function. Recently, several RBPs containing K Homology (KH) RNA binding domains were shown to work with miRNAs to regulate gene expression, raising the possibility that KH domains may be important for coordinating with miRNA pathways in gene expression regulation. To ascertain whether additional KH domain proteins functionally interact with miRNAs during Caenorhabditis elegans development, we knocked down twenty-four genes encoding KH-domain proteins in several miRNA sensitized genetic backgrounds. Here, we report that a majority of the KH domain-containing genes genetically interact with multiple miRNAs and Argonaute alg-1. Interestingly, two KH domain genes, predicted splicing factors sfa- and asd-2, genetically interacted with all of the miRNA mutants tested, while other KH domain genes exhibited functional interactions only with specific miRNAs. Our domain architecture and phylogenetic relationship analyses of the C. elegans KH domain-containing proteins revealed potential groups that may share both structure and function. Collectively, we show that many C. elegans KH domain RBPs functionally interact with miRNAs, suggesting direct or indirect coordination between these two classes of post-transcriptional gene expression regulators.

中文翻译：

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包含KH域的RNA结合蛋白与microRNA协同调节秀丽隐杆线虫的发育

microRNA（miRNA）和RNA结合蛋白（RBP）在转录后水平上调控基因表达，但是人们对这些基因表达的关键调控因子之间协调的程度及其协调的精确机制尚不甚了解。RNA结合蛋白通常具有与特定蛋白功能相关的可识别的RNA结合域。最近，一些含有K同源性（KH）RNA结合结构域的RBPs被证明可与miRNA一起调节基因表达，从而增加了KH结构域可能对协调miRNA通路在基因表达调节中的作用。在秀丽隐杆线虫期间，确定其他KH结构域蛋白是否与miRNA功能相互作用在发展过程中，我们在几个miRNA敏感的遗传背景中敲除了编码KH域蛋白的24个基因。在这里，我们报告大多数包含KH域的基因与多个miRNA和Argonaute alg-1发生遗传相互作用。有趣的是，两个KH域基因，即预测的剪接因子sfa-和asd-2，与所有测试的miRNA突变体发生了遗传相互作用，而其他KH域基因仅与特定的miRNA表现出功能性相互作用。我们的域结构和线虫KH域包含蛋白质的系统发育关系分析揭示了可能共享结构和功能的潜在基团。总的来说，我们显示了许多秀丽隐杆线虫 KH结构域RBP在功能上与miRNA相互作用，表明这两种转录后基因表达调节剂之间具有直接或间接的协调作用。