A genome-wide survey of sexually dimorphic expression of Drosophila miRNAs identifies the steroid hormone-induced miRNA let-7 as a regulator of sexual identity.

A genome-wide survey of sexually dimorphic expression of Drosophila miRNAs identifies the steroid hormone-induced miRNA let-7 as a regulator of sexual identity.
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对果蝇 miRNA 性别二态性表达的全基因组调查发现,类固醇激素诱导的 miRNA let-7 是性别认同的调节因子。

DOI:
10.1534/genetics.114.169268
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发表时间:
2014-10
期刊:
影响因子:
3.3
通讯作者:
Shcherbata HR
Shcherbata HR
中科院分区:
生物学2区
文献类型:
--
作者:
Fagegaltier D;König A;Gordon A;Lai EC;Gingeras TR;Hannon GJ;Shcherbata HR

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miRNAs在整个发育过程中以及在衰老的成年人中具有越来越多的功能。在这里,我们解决他们的作用,建立性二型性状和性别身份的男性和女性果蝇。我们对每个性别的miRNA群体的调查确定了在不同发育阶段的男性和女性组织中差异表达的miRNA组。普遍存在的miRNAs性别偏好表达通常随着组织的复杂性和性二态性而增加,性腺揭示了最显著的偏好。我们发现,男性特异性调节的X染色体是相关的miRNA表达在两个水平上。首先,在男性性腺中,偏向睾丸的miRNA倾向于位于X染色体上。第二,在索马中,X连锁的miRNA并不系统地依赖于剂量补偿。我们着手解决的重要性,在建立性二型性状的性别偏见表达的miRNA。我们的研究保守的let-7-C miRNA簇控制的性别偏向激素蜕皮激素的地方let-7作为性别决定层次的主要调制器。具有修饰let-7水平的果蝇呈现出双性生殖相关的表型,并表达通常仅限于异性的性别决定基因。在睾丸和卵巢中,蜕皮激素诱导let-7的改变导致性腺体细胞行为异常和早期生殖细胞分化的非细胞自主缺陷。性腺缺陷以及性别决定基因的异常表达在激素控制下的老年人中持续存在。总之,我们的研究结果将蜕皮激素和let-7视为体细胞系统信号的调节剂,有助于建立和维持男性和女性的性身份以及性腺的分化。这项工作为miRNAs在性二型性中的作用奠定了基础,并证明了果蝇中存在类似于脊椎动物的激素控制细胞性身份的作用。
MiRNAs bear an increasing number of functions throughout development and in the aging adult. Here we address their role in establishing sexually dimorphic traits and sexual identity in male and female Drosophila. Our survey of miRNA populations in each sex identifies sets of miRNAs differentially expressed in male and female tissues across various stages of development. The pervasive sex-biased expression of miRNAs generally increases with the complexity and sexual dimorphism of tissues, gonads revealing the most striking biases. We find that the male-specific regulation of the X chromosome is relevant to miRNA expression on two levels. First, in the male gonad, testis-biased miRNAs tend to reside on the X chromosome. Second, in the soma, X-linked miRNAs do not systematically rely on dosage compensation. We set out to address the importance of a sex-biased expression of miRNAs in establishing sexually dimorphic traits. Our study of the conserved let-7-C miRNA cluster controlled by the sex-biased hormone ecdysone places let-7 as a primary modulator of the sex-determination hierarchy. Flies with modified let-7 levels present doublesex-related phenotypes and express sex-determination genes normally restricted to the opposite sex. In testes and ovaries, alterations of the ecdysone-induced let-7 result in aberrant gonadal somatic cell behavior and non-cell-autonomous defects in early germline differentiation. Gonadal defects as well as aberrant expression of sex-determination genes persist in aging adults under hormonal control. Together, our findings place ecdysone and let-7 as modulators of a somatic systemic signal that helps establish and sustain sexual identity in males and females and differentiation in gonads. This work establishes the foundation for a role of miRNAs in sexual dimorphism and demonstrates that similar to vertebrate hormonal control of cellular sexual identity exists in Drosophila.
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