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Updated: Jun 19, 2026

Extracellular Vesicle Tissue Factor Activity Assay
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Extracellular Vesicle Tissue Factor Activity Assay

Published on: December 29, 2023

Antagonistic roles of four SR proteins in the biosynthesis of alternatively spliced tissue factor transcripts in

Sajiv Chandradas1, Gintaras Deikus, Jonathan G Tardos

  • 1Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.

Journal of Leukocyte Biology
|October 22, 2009
PubMed

Insights

Researchers identified key proteins that control tissue factor (TF) production in monocytes. Modulating these splicing factors could lead to new therapies for TF-related conditions.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Peripheral blood monocytes express tissue factor (TF), a molecule involved in coagulation, inflammation, and tissue remodeling.
  • Two forms of TF exist: full-length transmembrane TF (flTF) and alternatively spliced soluble TF (asTF).
  • TF biosynthesis is regulated by alternative pre-mRNA splicing of exon 5.

Purpose of the Study:

  • To investigate the role of SR proteins in regulating TF exon 5 splicing in human monocytes.
  • To identify specific SR proteins that promote or inhibit TF exon 5 inclusion.
  • To understand the unique characteristics of the intron preceding TF exon 5.

Main Methods:

  • Development of a splicing reporter system to study TF pre-mRNA splicing.
  • Analysis of SR protein binding sites within TF exon 5.
  • Characterization of the intron preceding TF exon 5.

Main Results:

  • SR proteins ASF/SF2 and SRp55 promote TF exon 5 inclusion, leading to flTF production.
  • SR proteins SRp40 and SC35 antagonize ASF/SF2 and SRp55, promoting TF exon 5 exclusion and asTF production.
  • The intron preceding TF exon 5 exhibits unusual characteristics for U2 introns.

Conclusions:

  • SR protein activity can be modulated to control TF pre-mRNA splicing.
  • Targeting SR proteins offers a potential therapeutic strategy to modulate the TF profile in monocytes/macrophages.
  • Findings provide insights into the regulation of alternative splicing in immune cells.

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