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

IScience
Yosuke KadotaMasaki Mori

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.

Citations

Feb 11, 2021·Wiley Interdisciplinary Reviews. RNA·Brittany Lynn Angarola, Olga Anczuków
Oct 24, 2020·Scientific Reports·Faidruz Azura JamMasaki Mori
Mar 16, 2021·Frontiers in Endocrinology·Panyisha WuNicholas J G Webster
Apr 23, 2021·PloS One·Takao MorimuneMasaki Mori

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Methods Mentioned

BETA
PCR
transfection
RNA-seq
immunoprecipitation

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