Naro Chiara, Jolly Ariane, Di Persio Sara, Bielli Pamela, Setterblad Niclas, Alberdi Antonio J, Vicini Elena, Geremia Raffaele, De la Grange Pierre, Sette Claudio
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; Laboratories of Neuroembryology, Fondazione Santa Lucia IRCCS, 00143 Rome, Italy.
GenoSplice Technology, iPEPS-ICM, Hôpital de la Pitié Salpêtrière, 75013 Paris, France.
Dev Cell. 2017 Apr 10;41(1):82-93.e4. doi: 10.1016/j.devcel.2017.03.003. Epub 2017 Mar 30.
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.
精子发生过程中的全转录组重编程确保了雄性生殖细胞分化各阶段因子的适时表达。精母细胞和精子细胞需要对基因表达进行特别广泛的重编程,以从有丝分裂转换到减数分裂,并支持配子形态发生。在此,我们揭示了这种减数分裂分化过程中广泛的可变剪接程序。值得注意的是,内含子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水平的保留。保留的内含子具有较弱的剪接位点,并且在与配子功能密切相关的基因中富集。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,它们是稳定的RNA,半衰期比正确剪接的转录本更长。引人注目的是,命运映射实验表明,IRT在合成数天后被招募到多核糖体上。这些研究揭示了调控内含子保留在精子发生过程中调节特定转录本适时表达方面的意外功能。