Srsf7 Establishes the Juvenile Transcriptome through Age-Dependent Alternative Splicing in Mice

Yosuke Kadota; Faidruz Azura Jam; Haruka Yukiue; Ichiro Terakado; Takao Morimune; Ayami Tano; Yuya Tanaka; Sayumi Akahane; Mayu Fukumura; Ikuo Tooyama; Masaki Mori

doi:10.1016/j.isci.2020.100929

Srsf7 Establishes the Juvenile Transcriptome through Age-Dependent Alternative Splicing in Mice

iScience. 2020 Mar 27;23(3):100929. doi: 10.1016/j.isci.2020.100929. Epub 2020 Feb 22.

Authors

Affiliations

¹ Molecular Neuroscience Research Center (MNRC), Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
² Research Center for Animal Life Science (RCALS), Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
³ Molecular Neuroscience Research Center (MNRC), Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan; Department of Pediatrics, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
⁴ Molecular Neuroscience Research Center (MNRC), Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan. Electronic address: morim@belle.shiga-med.ac.jp.

Abstract

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.

Keywords: Developmental Genetics; Molecular Biology.