Native tertiary structure and nucleoside modifications suppress tRNA's intrinsic ability to activate the innate immune sensor PKR.

Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation.

RNA helical imperfections regulate activation of the protein kinase PKR: effects of bulge position, size, and geometry.

The protein kinase, PKR, is activated by long stretches of double-stranded (ds) RNA. Viruses often make long dsRNA elements with imperfections that still activate PKR. However, due to the complexity of the RNA structure, prediction of whether a given RNA is an activator of PKR is difficult.

Regulation of innate immunity through RNA structure and the protein kinase PKR.

Molecular recognition of RNA structure is key to innate immunity. The protein kinase PKR differentiates self from non-self by recognition of molecular patterns in RNA. Certain biological RNAs induce autophosphorylation of PKR, activating it to phosphorylate eukaryotic initiation factor 2α (eIF2α), which leads to inhibition of translation.

Regulation of PKR by HCV IRES RNA: importance of domain II and NS5A.

Protein kinase R (PKR) is an essential component of the innate immune response. In the presence of double-stranded RNA (dsRNA), PKR is autophosphorylated, which enables it to phosphorylate its substrate, eukaryotic initiation factor 2alpha, leading to translation cessation. Typical activators of PKR are long dsRNAs produced during viral infection, although certain other RNAs can also activate.

RNA dimerization promotes PKR dimerization and activation.

The double-stranded RNA (dsRNA)-activated protein kinase [protein kinase R (PKR)] plays a major role in the innate immune response in humans. PKR binds dsRNA non-sequence specifically and requires a minimum of 15-bp dsRNA for one protein to bind and 30-bp dsRNA to induce protein dimerization and activation by autophosphorylation. PKR phosphorylates eukaryotic initiation factor 2alpha, a translation initiation factor, resulting in the inhibition of protein synthesis.

Combinatorial synthesis of thrombin-binding aptamers containing iso-guanine.

A library of all possible substitutions of guanine by iso-guanine (iG) in the thrombin aptamer was prepared by split and mix synthesis. A colorimetric assay was used to screen for functional oligomers in the library. Colorimetrically active oligonucleotides were selected and sequenced by the Maxam-Gilbert method.

A brilliant disguise for self RNA: 5'-end and internal modifications of primary transcripts suppress elements of innate immunity.

Interferon inducible protein kinase PKR is a component of innate immunity and mediates antiviral actions by recognizing pathogen associated molecular patterns (PAMPs). A well-known activator of PKR is long dsRNA, which can be produced during viral replication. Our recent results indicate that PKR can also be activated by short stem-loop RNA in a 5'-triphosphate-dependent fashion.

Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner.

The human interferon-induced protein kinase PKR is a key component of innate immunity, a process in which it senses pathogenic RNA. PKR consists of an N-terminal dsRNA-binding domain (dsRBD) and a C-terminal kinase domain. Upon binding long (>33 base pairs) stretches of pathogenic dsRNA, PKR undergoes autophosphorylation, which activates it to phosphorylate eIF2alpha, leading to inhibition of translation initiation.

5'-triphosphate-dependent activation of PKR by RNAs with short stem-loops.

Molecular patterns in pathogenic RNAs can be recognized by the innate immune system, and a component of this response is the interferon-induced enzyme RNA-activated protein kinase (PKR). The major activators of PKR have been proposed to be long double-stranded RNAs. We report that RNAs with very limited secondary structures activate PKR in a 5'-triphosphate-dependent fashion in vitro and in vivo.