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Using the E1A Minigene Tool to Study mRNA Splicing Changes
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SRRM2 organizes splicing condensates to regulate alternative splicing.

Shaohai Xu1, Soak-Kuan Lai1, Donald Yuhui Sim1

  • 1School of Biological Sciences, Nanyang Technological University, 637551 Singapore.

Nucleic Acids Research
|August 5, 2022
PubMed
Summary

SRRM2 protein forms liquid-like condensates, organizing nuclear speckles and regulating alternative splicing. SRRM2 dysfunction impacts cell viability, immunity, and cancer, highlighting its role in cell homeostasis.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • SRRM2 is a nuclear-speckle marker with disordered domains implicated in human diseases.
  • Dysfunction of SRRM2 is linked to various pathological conditions.

Purpose of the Study:

  • To investigate the biophysical properties and cellular functions of SRRM2.
  • To elucidate the role of SRRM2 in nuclear speckle organization and alternative splicing.

Main Methods:

  • Utilized EGFP-SRRM2 knock-in HEK293T cells for live-cell imaging.
  • Performed in vitro experiments to assess liquid-liquid phase separation hallmarks.
  • Investigated SRRM2 depletion effects in THP-1 myeloid-like cells.

Main Results:

  • SRRM2 forms liquid-like biomolecular condensates with characteristic phase separation properties.
  • SRRM2 organizes nuclear speckles throughout the cell cycle and acts as a splicing factor.
  • SRRM2 deficiency alters alternative splicing, affects cell viability, promotes differentiation, and influences inflammatory responses and oncogenic MUC1 isoforms.

Conclusions:

  • SRRM2 functions as a scaffold protein that organizes nuclear speckles.
  • SRRM2 plays a critical role in regulating alternative splicing in innate immunity and maintaining cell homeostasis.
  • SRRM2's involvement in disease pathogenesis warrants further investigation.