Related Experiment Video
Updated: Sep 26, 2026

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
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.
Abstract:
We have identified a cDNA (named C114) that encodes novel transcripts induced by IL-11 in mouse 3T3 L1 cells. Northern analysis of RNAs from multiple mouse tissues detects two C114 transcripts of approximately 1.0 and approximately 2.0 kb with the highest expression in liver, testis, brain, and kidney. The C114 cDNA contains an open reading frame of 187 amino acids with a predicted mass of 21 kDa. Three putative nuclear localization signals are predicted at amino acids 83-88, 126-131, and 167-178. Using green fluorescent protein (GFP)-C114 fusion plasmids, amino acids 126-131 are shown to be essential for the nuclear localization of C114. An arginine-rich region (amino acids 98-143) spanning the nuclear localization signals (amino acids 126-131) exhibits a double-stranded RNA (dsRNA) binding activity. Competition experiments with different RNA homopolymers demonstrate that C114 preferentially binds to poly(I.C). Similar to other dsRNA-binding proteins, C114 binds to the dsRNA-activated protein kinase, protein kinase R (PKR), via dsRNA-binding domains of PKR and the N-terminal region of the C114 protein. In vitro kinase assays indicate that C114 inhibits PKR activation via a dsRNA-independent mechanism. Overexpression of C114 protein inhibits the induction of eIF-2alpha phosphorylation following poly(I.C) treatment. This is the first demonstration of a novel PKR modulator induced by a gp130 superfamily cytokine that may play a role in cytokine-mediated biological functions.
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.
Related Concept Videos
Experimental RNAi
Inhibition of Cdk Activity
Negative Regulator Molecules
RNA Interference
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
MAPK Signaling Cascades
Inhibitors of Viral Protein Synthesis
