Identification of RNase L-Dependent, 3'-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells

Girardi, Erika; Chane-Woon-Ming, Béatrice; Messmer, Mélanie; Kaukinen, Pasi; Pfeffer, Sébastien

To date, SINV has not been shown to give rise to any small RNA species in mammalian cells. As such, we decided to investigate the small RNA profile of SINV-infected human and African green monkey cell lines. Using small RNA cloning and deep sequencing techniques, we provide evidence that the SINV genome is a source of small RNAs in infected mammalian cells. Some of these small RNAs accumulate to levels detected by Northern blot analysis. We set out to identify the factors involved in their biogenesis and show that they do not depend on the RNA silencing machinery, but rather, that they are downstream products of the cytoplasmic IFN-induced endoribonuclease RNase L. Finally, we also present experimental evidence that these viral small RNAs are modified at their 3= extremity. Altogether, our results indicate that the SINV-derived small RNAs could represent key markers of the host defense mechanism.