Kadota Yosuke, Jam Faidruz Azura, Yukiue Haruka, Terakado Ichiro, Morimune Takao, Tano Ayami, Tanaka Yuya, Akahane Sayumi, Fukumura Mayu, Tooyama Ikuo, Mori Masaki
Molecular Neuroscience Research Center (MNRC), Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Research Center for Animal Life Science (RCALS), Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
iScience. 2020 Mar 27;23(3):100929. doi: 10.1016/j.isci.2020.100929. Epub 2020 Feb 22.
The juvenile phase is characterized by continuously progressing physiological processes such as growth and maturation, which are accompanied by transitions in gene expression. The contribution of transcriptome dynamics to the establishment of juvenile properties remains unclear. Here, we investigated alternative splicing (AS) events in postnatal growth and elucidated the landscape of age-dependent alternative splicing (ADAS) in C57BL/6 mice. Our analysis of ADAS in the cerebral cortex, cardiomyocytes, and hepatocytes revealed numerous juvenile-specific splicing isoforms that shape the juvenile transcriptome, which in turn functions as a basis for the highly anabolic status of juvenile cells. Mechanistically, the juvenile-expressed splicing factor Srsf7 mediates ADAS, as exemplified by switching from juvenile to adult forms of anabolism-associated genes Eif4a2 and Rbm7. Suppression of Srsf7 results in "fast-forwarding" of this transcriptome transition, causing impaired anabolism and growth in mice. Thus, juvenile-specific AS is indispensable for the anabolic state of juveniles and differentiates juveniles from adults.
幼年期的特征是持续进行的生理过程，如生长和成熟，这些过程伴随着基因表达的转变。转录组动态变化对幼年期特性建立的贡献仍不清楚。在这里，我们研究了出生后生长过程中的可变剪接（AS）事件，并阐明了C57BL/6小鼠中年龄依赖性可变剪接（ADAS）的情况。我们对大脑皮层、心肌细胞和肝细胞中的ADAS分析揭示了许多塑造幼年期转录组的幼年期特异性剪接异构体，而幼年期转录组又作为幼年期细胞高度合成代谢状态的基础发挥作用。从机制上讲，幼年期表达的剪接因子Srsf7介导ADAS，以合成代谢相关基因Eif4a2和Rbm7从幼年期形式转变为成年期形式为例。抑制Srsf7会导致这种转录组转变的“加速”，导致小鼠合成代谢受损和生长受阻。因此，幼年期特异性AS对于幼年期的合成代谢状态是不可或缺的，并且使幼年期与成年期区分开来。
