Retinoblastoma proteins are eukaryotic transcriptional corepressors that play central roles in cell cycle control, among other functions. Although most metazoan genomes encode a single retinoblastoma protein, gene duplications have occurred at least twice: in the vertebrate lineage, leading to Rb, p107, and p130, and in Drosophila, an ancestral Rbf1 gene and a derived Rbf2 gene. Structurally, Rbf1 resembles p107 and p130, and mutation of the gene is lethal. Rbf2 is more divergent and mutation does not lead to lethality. However, the retention of Rbf2 >60 My in Drosophila points to essential functions, which prior cell-based assays have been unable to elucidate. Here, using genomic approaches, we provide new insights on the function of Rbf2. Strikingly, we show that Rbf2 regulates a set of cell growth-related genes and can antagonize Rbf1 on specific genes. These unique properties have important implications for the fly; Rbf2 mutants show reduced egg laying, and lifespan is reduced in females and males. Structural alterations in conserved regions of Rbf2 gene suggest that it was sub- or neofunctionalized to develop specific regulatory specificity and activity. We define cis-regulatory features of Rbf2 target genes that allow preferential repression by this protein, indicating that it is not a weaker version of Rbf1 as previously thought. The specialization of retinoblastoma function in Drosophila may reflect a parallel evolution found in vertebrates, and raises the possibility that cell growth control is equally important to cell cycle function for this conserved family of transcriptional corepressors.

中文翻译：

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与顺式和反式适应相关的视网膜母细胞瘤蛋白功能的多样化。

视网膜母细胞瘤蛋白是真核转录的核心表达因子，除其他功能外，在细胞周期控制中起着核心作用。尽管大多数后生动物的基因组只编码一个视网膜母细胞瘤蛋白，但基因重复至少发生过两次：在脊椎动物谱系中，导致Rb，p107和p130；在果蝇中，祖先的Rbf1基因和一个衍生的Rbf2基因。在结构上，Rbf1类似于p107和p130，该基因的突变具有致死性。Rbf2更趋异，突变不会导致致命性。然而，Rbf2> 60 My在果蝇中的保留表明基本功能，以前的基于细胞的测定法无法阐明。在这里，我们使用基因组学方法，对Rbf2的功能提供了新的见解。惊人地 我们显示Rbf2调节了一组与细胞生长相关的基因，并且可以拮抗特定基因上的Rbf1。这些独特的特性对飞行具有重要的意义。Rbf2突变体显示产卵减少，雌性和雄性寿命缩短。Rbf2基因保守区的结构改变表明，它被亚功能化或新功能化，以发展特定的调节特异性和活性。我们定义了Rbf2靶基因的顺式调节功能，允许该蛋白优先抑制，表明它不是以前认为的Rbf1的弱版本。果蝇中视网膜母细胞瘤功能的特殊化可能反映了脊椎动物中的平行进化，