C114 is a novel IL-11-inducible nuclear double-stranded RNA-binding protein that inhibits protein kinase R

Zhan Yin1, Jennifer Haynie, Bryan R G Williams

  • 1Department of Pharmacology and Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4965, USA.

Insights

Researchers discovered a new protein, C114, induced by IL-11. This double-stranded RNA-binding protein inhibits protein kinase R (PKR) activation, potentially influencing cytokine-mediated functions.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Interleukin-11 (IL-11) is a cytokine involved in various biological processes.
  • Understanding novel transcripts induced by cytokines is crucial for elucidating cellular responses.

Purpose of the Study:

  • To identify and characterize novel transcripts induced by IL-11.
  • To investigate the function and interactions of the identified C114 protein.

Main Methods:

  • Northern blot analysis to detect C114 transcripts in mouse tissues.
  • Green fluorescent protein (GFP) fusion plasmids to determine nuclear localization signals.
  • RNA binding assays and protein interaction studies with protein kinase R (PKR).

Main Results:

  • A novel cDNA, C114, encoding a 21 kDa protein with nuclear localization signals was identified.
  • C114 exhibits double-stranded RNA (dsRNA) binding activity, preferentially binding to poly(I:C).
  • C114 inhibits PKR activation through a dsRNA-independent mechanism and reduces eIF-2alpha phosphorylation.

Conclusions:

  • C114 is a novel PKR modulator induced by IL-11.
  • C114 may play a significant role in cytokine-mediated biological functions.
  • This discovery opens new avenues for understanding cellular signaling pathways regulated by cytokines.

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