An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation.
An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation.
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DOI：
10.1016/j.devcel.2017.03.003
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发表时间：
2017-04-10
影响因子：
11.8
通讯作者：
Sette C
中科院分区：
文献类型：
--
作者：
Naro C;Jolly A;Di Persio S;Bielli P;Setterblad N;Alberdi AJ;Vicini E;Geremia R;De la Grange P;Sette C
精子发生过程中的全局转录组重新编程确保了在男性生殖细胞分化的每个阶段及时表达因子。精母细胞和精子细胞需要特别广泛的基因表达重新编程，以从有丝分裂切换到减数分裂，并支持配子的形态发生。在这里，我们发现了在这种跨减数分裂分化过程中广泛的选择性剪接程序。值得注意的是，内含子的保留在很大程度上是最丰富的模式，与精子细胞相比，精母细胞通常表现出更高的保留水平。保留的内含子以弱剪接位点为特征，富含与配子功能密切相关的基因。减数分裂内含子保留转录本(IRT)仅定位于细胞核。然而，与其他发育调控的IRT不同的是，它们是稳定的RNA，表现出比正确剪接的转录本更长的半衰期。引人注目的是，命运图实验显示，IRT在合成几天后就被招募到多聚核糖体上。这些研究揭示了在精子发生过程中，调控内含子保留在调节选定转录本的及时表达方面具有意想不到的功能。在减数分裂的精母细胞中，选择性剪接有利于内含子的保留，内含子的保留稳定了减数分裂精母细胞中核转录的稳定性。在减数分裂过程中，高的转录速率超过了弱内含子的剪接体。在哺乳动物的精子发生过程中，长寿命的内含子保留的mRNAs编码了雄性配子功能转录的关键蛋白。Naro等人。研究表明，在雄性减数分裂生殖细胞中，受调控的内含子保留会产生长寿的内含子保留转录本，这些转录本在合成后保存数天，并可以被转录不活跃的减数分裂后生殖细胞及时翻译。
Global transcriptome reprogramming during spermatogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Spermatocytes and spermatids require particularly extensive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete function. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis. Alternative splicing in meiotic spermatocytes favors intron retention Intron retention stabilizes nuclear transcripts in meiotic spermatocytes A high transcription rate outcompetes the spliceosome from weak introns in meiosis Long-lived intron-retaining mRNAs encode key proteins for male gamete function Transcription during mammalian spermatogenesis is discontinuous and ceases in late post-meiotic stages. Naro et al. show that regulated intron retention in male meiotic germ cells generates long-lived intron-retaining transcripts that are preserved for days after their synthesis and can be timely translated by transcriptionally inactive post-meiotic germ cells.