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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
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Linking Endoplasmic Reticular Stress and Alternative Splicing.

Nolan T Carew1, Ashley M Nelson2, Zhitao Liang3

  • 1School of Medicine, Department of Immunology, University of Pittsburgh, E1059 Biomedical Science Tower, Pittsburgh, PA 15261, USA. ntc8@pitt.edu.

International Journal of Molecular Sciences
|December 15, 2018
PubMed
Summary
This summary is machine-generated.

Endoplasmic reticulum stress and ELL2 influence RNA splicing in antibody-secreting cells. These processes are critical for immunoglobulin secretion and cellular responses to stimuli like lipopolysaccharide.

Keywords:
B cellsER stressRIDDRNA splicingunfolded protein response

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Endoplasmic reticulum (ER) stress triggers the unfolded protein response (UPR), a survival mechanism involving gene regulation.
  • The kinase Ire1, activated by ER stress, exhibits mRNA decay activity and non-canonical splicing of Xbp1 mRNA.
  • B cell activation by lipopolysaccharide (LPS) rapidly induces Ire1 phosphorylation, altering mRNA content and splicing.

Purpose of the Study:

  • To investigate the role of ER stress, ELL2, and snRNAs in shaping RNA splicing patterns during antibody secretion.
  • To understand the dynamic changes in mRNA splicing following B cell activation and their persistence.
  • To elucidate the function of ELL2 in immunoglobulin secretion and its impact on mRNA processing.

Main Methods:

  • Stimulation of naïve splenic B cells with LPS.
  • Analysis of mRNA splicing patterns at early (18 h) and late (72 h) stages post-stimulation.
  • Investigating the impact of inhibiting Ire1's mRNA degradation function.
  • Assessing the role of ELL2 in immunoglobulin secretion and mRNA processing.

Main Results:

  • LPS stimulation induces widespread mRNA splicing changes in B cells, with some persisting for up to 72 hours.
  • Inhibition of Ire1's mRNA decay function alters splicing patterns and reduces snRNA transcription factors.
  • ELL2 upregulation introduces new splicing changes and is essential for immunoglobulin secretion, affecting over 5000 genes.
  • Over 4000 splicing changes were observed 18 hours after LPS stimulation.

Conclusions:

  • RNA splicing in antibody-secreting cells is dynamically regulated by ER stress, Ire1 activity, and ELL2 induction.
  • ELL2 plays a critical role in immunoglobulin secretion by modulating mRNA processing.
  • These splicing alterations are integral to the cellular response and function of antibody-secreting cells.