Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that autosomal testis-biased miRNAs tend to be somatically male-biased, whereas autosomal ovary-biased miRNAs are female-biased, possibly due to broad hormonal control. In chicken, which has a Z/W sex chromosome system, expression output of genes on the Z Chromosome is expected to be male-biased, since there is no global dosage compensation mechanism that restores expression in ZW females after almost all genes on the W Chromosome decayed. Nevertheless, we found that the dominant liver miRNA, miR-122-5p, is Z-linked but expressed in an unbiased manner, due to the unusual retention of a W-linked copy. Another Z-linked miRNA, the male-biased miR-2954-3p, shows conserved preference for dosage-sensitive genes on the Z Chromosome, based on computational and experimental data from chicken and zebra finch, and acts to equalize male-to-female expression ratios of its targets. Unexpectedly, our findings thus establish miRNA regulation as a novel gene-specific dosage compensation mechanism.

性别二态性取决于性别偏见的基因表达，但尚未对 microRNA (miRNA) 的贡献进行全球评估。因此，我们生成了广泛的小 RNA 测序数据集，用于分析小鼠、负鼠和鸡的雄性和雌性 miRNA 表达谱。我们的分析发现了许多体细胞性别偏向 miRNA 表达的案例，其中在小鼠心脏和肝脏中发现的比例最大。性别偏见的表达可以通过 miRNA 特异性调控来解释，包括启动子处的性别偏见染色质可及性，而不是在性别偏见的蛋白质编码基因上搭载内含子 miRNA。在小鼠中，但不是负鼠和鸡，性别偏见是跨组织协调的，因此常染色体睾丸偏向 miRNA 倾向于体细胞男性偏向，而常染色体卵巢偏向 miRNA 偏向女性，可能是由于广泛的荷尔蒙控制。在具有 Z/W 性染色体系统的鸡中，Z 染色体上基因的表达输出预计是男性偏向的，因为没有全局剂量补偿机制可以在 W 上几乎所有基因之后恢复 ZW 雌性的表达染色体腐烂。尽管如此，我们发现显性肝脏 miRNA miR-122-5p 是 Z 连锁的，但由于 W 连锁拷贝的异常保留，以无偏的方式表达。另一种 Z-连锁 miRNA，雄性偏向性 miR-2954-3p，基于来自鸡和斑胸草雀的计算和实验数据，对 Z 染色体上的剂量敏感基因表现出保守的偏好，并起到平衡雄性与雌性的作用其靶标的表达率。不料，