Srsf7-Mutant mice organ

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 incompletely understood. Here, we investigated alternative splicing (AS) events in postnatal growth and elucidated the landscape of age-dependent alternative splicing (ADAS). 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 the switching from juvenile to adult forms of the anabolism-associated genes Eif4a2 and Rbm7. Suppression of Srsf7 results in "fast-forwarding" of this transcriptome transition, causing impaired cellular anabolism and growth in mice. Thus, juvenile-specific AS is indispensable for the anabolic state of juveniles; these findings shed light on the role of AS in differentiating juveniles from adults.