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SRSF2 promotes splicing and transcription of exon 11 included isoform in Ron proto-oncogene

Heegyum Moon1, Sunghee Cho1, Tiing Jen Loh1

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

Biochimica Et Biophysica Acta
|September 16, 2014
PubMed

Insights

SRSF2 regulates the inclusion of exon 11 in the Ron proto-oncogene, affecting its expression. This splicing factor targets exon 11, influencing Ron protein levels and function.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cancer Research

Background:

  • The proto-oncogene Ron encodes a receptor tyrosine kinase involved in cell motility.
  • Aberrant Ron expression, particularly the constitutively active Ron△165 isoform due to exon 11 skipping, is linked to cancer progression.
  • Understanding the regulation of Ron splicing is crucial for deciphering its role in disease.

Purpose of the Study:

  • To investigate the role of SRSF2 (Serine/Arginine-rich splicing factor 2) in regulating Ron pre-mRNA splicing.
  • To elucidate the mechanism by which SRSF2 controls exon 11 inclusion of the Ron gene.
  • To identify the specific sequence and interaction of SRSF2 with Ron exon 11.

Main Methods:

  • RNA interference (knockdown) and overexpression of SRSF2.
  • Analysis of pre-mRNA splicing patterns for Ron exon 11 and introns 10/11.
  • Mutation analysis of SRSF2 binding sites on Ron exon 11.
  • Assessment of SRSF2 physical interaction with target sequences.

Main Results:

  • Knockdown of SRSF2 decreased exon 11 inclusion, while its overexpression enhanced inclusion.
  • SRSF2 influences both splicing and transcription of the Ron gene.
  • SRSF2 directly binds to the CGAG sequence on Ron exon 11, promoting its inclusion.
  • The strength of splice sites flanking exon 11 is not essential for SRSF2-mediated splicing regulation.

Conclusions:

  • SRSF2 is a key regulator of Ron proto-oncogene expression by promoting exon 11 inclusion.
  • SRSF2 targets exon 11 directly, providing a novel mechanism for controlling Ron expression.
  • These findings offer insights into the molecular mechanisms governing oncogene expression and potential therapeutic targets.
Keywords:
Exon 11 inclusionPre-mRNA splicingProto-oncogeneRonSRSF2Transcription

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