文章基本信息

标题：Srsf7 Establishes the Juvenile Transcriptome through Age-Dependent Alternative Splicing in Mice
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作者：Yosuke Kadota ; Faidruz Azura Jam ; Haruka Yukiue 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：3
页码：1-37
DOI：10.1016/j.isci.2020.100929
语种：English
出版社：Elsevier
摘要：SummaryThe 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 genesEif4a2andRbm7. 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.Graphical AbstractDisplay OmittedHighlights•Age-dependent alternative splicing (ADAS) was determined in mice•Srsf7 depletion causes loss of cellular juvenescence•Srsf7 mutation causes a shift from juvenile to adult-type transcriptome•Srsf7 promotes juvenile growth and anabolism through ADASDevelopmental Genetics; Molecular Biology