IL-2 regulates the expression of the NK-TR gene via an alternate RNA splicing mechanism

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A Rinfret1, S K Anderson

  • 1National Research Council, Biotechnology Research Institute, Montréal, Québec, Canada.

Molecular Immunology
|October 1, 1993
PubMed

Insights

Researchers identified alternative splicing in the natural killer (NK) cell tumour-recognition protein (NK-TR) mRNA. Interleukin-2 (IL-2) activation of NK cells promotes splicing that increases complete NK-TR protein production.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Natural killer (NK) cells are crucial for innate immunity, recognizing and eliminating tumor cells.
  • A specific NK cell tumor-recognition protein (NK-TR) has been identified, encoded by a gene expressed in NK cells.
  • The NK-TR protein is a 150 kD molecule with a cyclophilin-related N-terminus and positively charged domains.

Purpose of the Study:

  • To investigate alternative splicing events in the NK-TR mRNA.
  • To determine the functional consequences of identified alternative splicing events on NK-TR protein production.
  • To examine the effect of Interleukin-2 (IL-2) activation on NK-TR mRNA splicing patterns.

Main Methods:

  • Gene and mRNA characterization of human and mouse NK-TR.
  • Analysis of alternative splicing in the 5' region of NK-TR mRNA.
  • Investigation of splicing changes following IL-2 activation of NK cells.

Main Results:

  • Two distinct alternative splicing events were discovered in the NK-TR mRNA.
  • One event introduces a 28 bp exon, causing a frameshift and premature termination of the NK-TR protein.
  • A second event deletes 25 amino acids from the NK-TR protein due to internal splice acceptor usage.
  • IL-2 activation of NK cells alters splicing, leading to increased production of mRNA encoding the complete NK-TR protein.

Conclusions:

  • Alternative splicing significantly impacts NK-TR protein expression and potentially its function.
  • IL-2 stimulation enhances the production of functional NK-TR protein by modulating mRNA splicing.
  • These findings provide insights into the regulation of NK-TR, a key protein in NK cell-mediated tumor recognition.

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