FIG. 1.

Signaling pathways of long dsRNAs in the cytoplasm. The major known pathways of signaling by long cytoplasmic dsRNAs are shown and are discussed in detail in the text. Most long cytoplasmic dsRNAs result from virus infections. Such dsRNAs can bind to and activate PKR and 2′,5′-AS as well as activating the interferon pathway. Activated PKR phosphorylates a number of targets, including the translation factor eIF2α and the IκB protein, leading to translation inhibition and effects on gene expression in the nucleus. Activated 2′,5′-AS leads to activation of RNase L, which degrades mRNAs. As discussed in the text, long dsRNAs can also lead to apoptosis.