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Real-time Live Imaging of T-cell Signaling Complex Formation
10:31

Real-time Live Imaging of T-cell Signaling Complex Formation

Published on: June 23, 2013

Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation

C Y Chen1, R Gherzi, J S Andersen

  • 1Department of Pharmacology, University of California San Diego, La Jolla, California 92093, USA.

Genes & Development
|May 19, 2000
PubMed

Insights

The JNK-signaling pathway stabilizes interleukin-2 (IL-2) mRNA during T-cell activation. Nucleolin and YB-1 proteins bind to the JNK response element (JRE) on IL-2 mRNA, mediating this stabilization.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Signaling

Background:

  • Regulated mRNA turnover is crucial for cellular function but not fully understood.
  • The JNK-signaling pathway's role in stabilizing interleukin-2 (IL-2) mRNA during T-cell activation was previously suggested.
  • A specific element in the IL-2 mRNA's 5' untranslated region (UTR), the JNK response element (JRE), was implicated.

Purpose of the Study:

  • To identify the RNA-binding proteins that interact with the JRE of IL-2 mRNA.
  • To elucidate the mechanism by which JNK signaling stabilizes IL-2 mRNA.
  • To understand the role of identified proteins in the formation of messenger ribonucleoprotein (mRNP) complexes.

Main Methods:

  • Utilized IL-2 mRNA as a model system for studying mRNA regulation.
  • Investigated the JNK-signaling pathway's effect on IL-2 mRNA stability.
  • Employed a cell-free system mimicking regulated mRNA decay.
  • Identified RNA-binding proteins through their interaction with the JRE.

Main Results:

  • Identified nucleolin and YB-1 as two major RNA-binding proteins that specifically bind to the JRE.
  • Demonstrated that binding of both nucleolin and YB-1 is essential for IL-2 mRNA stabilization induced by T-cell activation.
  • Confirmed that nucleolin and YB-1 mediate JNK-induced IL-2 mRNA stabilization in a cell-free system.
  • Showed that these proteins are required for forming an IL-2 mRNP complex responsive to stabilizing signals.

Conclusions:

  • Nucleolin and YB-1 are key mediators of IL-2 mRNA stabilization.
  • The JNK-signaling pathway, through nucleolin and YB-1 binding to the JRE, plays a critical role in regulating IL-2 mRNA turnover.
  • These findings provide new insights into the molecular mechanisms of mRNA stabilization during immune responses.

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