An antiviral response directed by PKR phosphorylation of the RNA helicase A.

Article Details

Citation

Sadler AJ, Latchoumanin O, Hawkes D, Mak J, Williams BR

An antiviral response directed by PKR phosphorylation of the RNA helicase A.

PLoS Pathog. 2009 Feb;5(2):e1000311. doi: 10.1371/journal.ppat.1000311. Epub 2009 Feb 20.

PubMed ID
19229320 [ View in PubMed
]
Abstract

The double-stranded RNA-activated protein kinase R (PKR) is a key regulator of the innate immune response. Activation of PKR during viral infection culminates in phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2alpha) to inhibit protein translation. A broad range of regulatory functions has also been attributed to PKR. However, as few additional PKR substrates have been identified, the mechanisms remain unclear. Here, PKR is shown to interact with an essential RNA helicase, RHA. Moreover, RHA is identified as a substrate for PKR, with phosphorylation perturbing the association of the helicase with double-stranded RNA (dsRNA). Through this mechanism, PKR can modulate transcription, as revealed by its ability to prevent the capacity of RHA to catalyze transactivating response (TAR)-mediated type 1 human immunodeficiency virus (HIV-1) gene regulation. Consequently, HIV-1 virions packaged in cells also expressing the decoy RHA peptides subsequently had enhanced infectivity. The data demonstrate interplay between key components of dsRNA metabolism, both connecting RHA to an important component of innate immunity and delineating an unanticipated role for PKR in RNA metabolism.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Interferon-induced, double-stranded RNA-activated protein kinaseP19525Details