A human cellular noncoding RNA activates the antiviral protein 2'-5'-oligoadenylate synthetase 1.
Brenda M CalderonGraeme L ConnPublished in: The Journal of biological chemistry (2018)
The 2'-5'-oligoadenylate synthetase (OAS) family of enzymes sense cytosolic dsRNA, a potent signal of viral infection. In response to dsRNA binding, OAS proteins synthesize the second messenger 2'-5'-linked oligoadenylate that activates the latent ribonuclease L (RNase L). RNase L-mediated degradation of viral and cellular RNAs effectively halts viral replication and further stimulates innate immune responses by inducing type I interferon. The OAS/RNase L pathway is therefore central in innate immune recognition and promotion of antiviral host responses. However, the potential for specific RNA sequences or structures to drive OAS1 activation and the molecular mechanisms by which they act are not currently fully understood. Moreover, the cellular regulators of OAS activity are not well defined. Here, we demonstrate that the human cellular noncoding RNA 886 (nc886) activates OAS1 both in vitro and in human A549 cells. We show that a unique structure present only in one of the two structural conformers adopted by nc886 drives potent OAS1 activation. In contrast, the conformer lacking this unique structure activated OAS1 only very weakly. We also found that formation of this OAS1-activating structural motif depends on the nucleotides in the apical-most loop of nc886 and the adjacent helix. These findings identify a cellular RNA capable of activating the OAS/RNase L pathway in human cells and illustrate the importance of structural elements, and their context, in potentiating OAS1 activity.
Keyphrases
- endothelial cells
- immune response
- sars cov
- magnetic resonance
- induced pluripotent stem cells
- signaling pathway
- computed tomography
- innate immune
- high resolution
- magnetic resonance imaging
- induced apoptosis
- dendritic cells
- transcription factor
- pluripotent stem cells
- small molecule
- risk assessment
- contrast enhanced
- endoplasmic reticulum stress
- human health