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SRSF9 Regulates Cassette Exon Splicing of Caspase-2 by Interacting with Its Downstream Exon

Jiyeon Ha1, Hana Jang1, Namjeong Choi1

  • 1School of life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.

Cells
|April 3, 2021
PubMed

Insights

Researchers identified SRS Family Member 9 (SRSF9) as a novel regulator of Caspase-2 alternative splicing (AS). SRSF9 controls the balance between pro-apoptotic and anti-apoptotic Caspase-2 mRNA isoforms by targeting a specific sequence in exon 10.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Alternative splicing (AS) is a crucial posttranscriptional regulatory mechanism.
  • Apoptosis, the process of programmed cell death, is vital for maintaining physiological homeostasis.
  • Caspase-2 pre-mRNA undergoes AS to produce both pro-apoptotic and anti-apoptotic mRNA isoforms, but its regulation is not fully understood.

Purpose of the Study:

  • To identify novel regulatory proteins involved in the alternative splicing of Caspase-2.
  • To elucidate the mechanism by which Caspase-2 alternative splicing is regulated.

Main Methods:

  • Knock-down (KD) and overexpression of SRS Family Member 9 (SRSF9).
  • Deletion and substitution mutagenesis of Caspase-2 pre-mRNA.
  • RNA-pulldown assays.
  • RNA sequencing (RNA-seq) and Gene Ontology (GO) analysis.

Main Results:

  • SRSF9 was identified as a novel regulator of Caspase-2 alternative splicing (AS).
  • SRSF9 KD increased cassette exon inclusion, while SRSF9 overexpression decreased it.
  • A specific AGGAG sequence in exon 10 was identified as the functional target for SRSF9 binding.
  • SRSF9 was shown to interact with this AGGAG sequence.
  • RNA-seq analysis revealed that SRSF9 regulates AS of other apoptosis-related genes.

Conclusions:

  • SRSF9 plays a critical role in regulating Caspase-2 alternative splicing.
  • The AGGAG sequence in exon 10 is essential for SRSF9-mediated regulation of Caspase-2 AS.
  • SRSF9 influences the balance of apoptosis-related gene splicing, impacting cellular processes.
Keywords:
SRSF9alternative splicingcaspase 2

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