Deep sequencing identifies noncanonical editing of Ebola and Marburg virus RNAs in infected cells.
Bottom Line: Further, we found that the well-characterized EBOV GP mRNA editing site is modified at a high frequency during viral genome RNA replication.Additionally, editing hot spots representing sites of apparent adenosine deaminase activity were found in the MARV-Ang NP 3'-untranslated region.These studies identify novel filovirus-host interactions and reveal production of a greater diversity of filoviral gene products than was previously appreciated.
Affiliation: Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.Show MeSH
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Mentions: There are no previous reports describing MARV mRNA editing. Therefore, we evaluated the MARV-Ang samples for regions of the genome prone to RNA editing. Of 20 homopolymer regions (6 or more identical nucleotides), our analysis identified two regions where insertions of additional As occurred at a high frequency. In each region, the number of sequencing reads with extra A residues within the homopolymer region were enumerated as described above for EBOV. One site in the NP mRNA (a 6-U repeat on the negative-sense vRNA between positions 816 and 821) had an extra-A insertion frequency of 11.73% (Vero cells) and 7.9% (Thp1 cells) at 24 hpi (Fig. 4A to C). A second region in the L mRNA (a 6-U repeat on the negative-sense vRNA at positions 17810 to 17815) was also identified with extra-A insertion frequencies of 16.54% in Vero cells and 19.54% in Thp1 cells at 24 hpi (Fig. 5A to C; see also Table S6 in the supplemental material). In both regions, editing events were specific to the mRNA, as insertion frequencies derived from amplicons specific for vRNA or plasmid DNA were at or below 1.00% (Fig. 4D to F and 5D to F; see also Table S6).
Affiliation: Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.