The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure

Martin, Baptiste; Coutard, Bruno; Guez, Théo; Paesen, Guido C; Canard, Bruno; Debart, Françoise; Vasseur, Jean-Jacques; Grimes, Jonathan M; Decroly, Etienne

The structure of the mRNA cap consists of a guanosine linked via a 5 -5 triphosphate bridge to the 5 end of newly synthetized RNA transcripts, and the cap is methylated at the N7 position of this guanosine and at the 2'O position of the first (n1) residue (24) . The cap is critical for virus replication as it protects viral mRNAs from cellular 5 exonucleases, allows the recruitment of the cellular eIF4e factor for translation initiation, and hides viral RNAs from detection by innate immunity sensors such as RIG-I and MDA5 and interferon induced restriction factors such as IFIT molecules (for review, see (25) ). The different enzymatic activities required for cap synthesis have already been characterized in mononegaviruses such as VSV (PRNTase and MTase activities) (17, 22) and hMPV (MTase activity) (26) . Strikingly, there is no biochemical or structural information on filovirus L proteins, likely because of difficulties in producing recombinant protein. Therefore, the capping process of filoviruses remained to be elucidated.