Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences

Agnes Karasik, Grant D Jones, Andrew V DePass, and Nicholas R Guydosh

Nucleic Acids Research, gkab036, https://doi.org/10.1093/nar/gkab036

Viral infections often trigger the activation of a ribonuclease produced by the host, RNase L, that cleaves single-stranded regions of viral and host RNAs and promotes clearance of the virus. Widespread cleavage of messenger RNAs (mRNAs) leads to broad reduction in their abundance but it remains unknown how this reduced pool of mRNAs is translated. The authors performed ribosome-profilingto globally assess the distribution of ribosomes in RNase L activated cells. Surprisingly, RNase L activation led to an increase in the relative translation of regions of the mRNA that are not normally translated. Since this alternative translational program was dependent on the catalytic activity of RNase L, the authors proposed a model where cleavage of mRNA by RNase L leads to the translation of mRNA fragments. The resulting cryptic peptides that are synthesized could be presented on the cell surface by MHC-I molecules as a “non-self” signal to enhance viral clearance.

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