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

Area of Science:

• Molecular Biology
• Developmental Biology
• Genomics

Background:

• The juvenile phase involves significant physiological changes, including growth and maturation.
• Gene expression transitions occur during development, but the role of transcriptome dynamics, particularly alternative splicing, is not fully understood.

Purpose of the Study:

• To investigate alternative splicing (AS) events during postnatal growth.
• To elucidate the landscape of age-dependent alternative splicing (ADAS) in mice.
• To understand the contribution of juvenile-specific AS to the anabolic status of juvenile cells.

Main Methods:

• Analysis of ADAS in the cerebral cortex, cardiomyocytes, and hepatocytes of C57BL/6 mice.
• Identification of juvenile-specific splicing isoforms.
• Investigation of the role of splicing factor Srsf7 in mediating ADAS.

Main Results:

• Numerous juvenile-specific splicing isoforms were identified, shaping the juvenile transcriptome.
• These isoforms contribute to the highly anabolic status characteristic of juvenile cells.
• The splicing factor Srsf7 was found to mediate ADAS, affecting anabolism-associated genes like Eif4a2 and Rbm7.
• Suppression of Srsf7 led to accelerated transcriptome transition, impaired anabolism, and growth defects in mice.

Conclusions:

• Juvenile-specific AS is essential for establishing and maintaining the anabolic state in juvenile animals.
• ADAS plays a critical role in differentiating juvenile and adult physiological states.
• Srsf7 is a key regulator of ADAS and juvenile growth.