Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure.
Ebolavirus (EBOV), the causative agent of a severe hemorrhagic fever and a biosafety level 4 pathogen, increases its genome coding capacity by producing multiple transcripts encoding for structural and nonstructural glycoproteins from a single gene. This is achieved through RNA editing, during which...
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Public Library of Science (PLoS)
2013
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oai:doaj.org-article:9a86172cb41f4c639f27d3a149d1d0d42021-11-18T06:07:27ZEbola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure.1553-73661553-737410.1371/journal.ppat.1003677https://doaj.org/article/9a86172cb41f4c639f27d3a149d1d0d42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24146620/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Ebolavirus (EBOV), the causative agent of a severe hemorrhagic fever and a biosafety level 4 pathogen, increases its genome coding capacity by producing multiple transcripts encoding for structural and nonstructural glycoproteins from a single gene. This is achieved through RNA editing, during which non-template adenosine residues are incorporated into the EBOV mRNAs at an editing site encoding for 7 adenosine residues. However, the mechanism of EBOV RNA editing is currently not understood. In this study, we report for the first time that minigenomes containing the glycoprotein gene editing site can undergo RNA editing, thereby eliminating the requirement for a biosafety level 4 laboratory to study EBOV RNA editing. Using a newly developed dual-reporter minigenome, we have characterized the mechanism of EBOV RNA editing, and have identified cis-acting sequences that are required for editing, located between 9 nt upstream and 9 nt downstream of the editing site. Moreover, we show that a secondary structure in the upstream cis-acting sequence plays an important role in RNA editing. EBOV RNA editing is glycoprotein gene-specific, as a stretch encoding for 7 adenosine residues located in the viral polymerase gene did not serve as an editing site, most likely due to an absence of the necessary cis-acting sequences. Finally, the EBOV protein VP30 was identified as a trans-acting factor for RNA editing, constituting a novel function for this protein. Overall, our results provide novel insights into the RNA editing mechanism of EBOV, further understanding of which might result in novel intervention strategies against this viral pathogen.Masfique MehediThomas HoenenShelly RobertsonStacy RicklefsMichael A DolanTravis TaylorDarryl FalzaranoHideki EbiharaStephen F PorcellaHeinz FeldmannPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 10, p e1003677 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Masfique Mehedi Thomas Hoenen Shelly Robertson Stacy Ricklefs Michael A Dolan Travis Taylor Darryl Falzarano Hideki Ebihara Stephen F Porcella Heinz Feldmann Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. |
| description |
Ebolavirus (EBOV), the causative agent of a severe hemorrhagic fever and a biosafety level 4 pathogen, increases its genome coding capacity by producing multiple transcripts encoding for structural and nonstructural glycoproteins from a single gene. This is achieved through RNA editing, during which non-template adenosine residues are incorporated into the EBOV mRNAs at an editing site encoding for 7 adenosine residues. However, the mechanism of EBOV RNA editing is currently not understood. In this study, we report for the first time that minigenomes containing the glycoprotein gene editing site can undergo RNA editing, thereby eliminating the requirement for a biosafety level 4 laboratory to study EBOV RNA editing. Using a newly developed dual-reporter minigenome, we have characterized the mechanism of EBOV RNA editing, and have identified cis-acting sequences that are required for editing, located between 9 nt upstream and 9 nt downstream of the editing site. Moreover, we show that a secondary structure in the upstream cis-acting sequence plays an important role in RNA editing. EBOV RNA editing is glycoprotein gene-specific, as a stretch encoding for 7 adenosine residues located in the viral polymerase gene did not serve as an editing site, most likely due to an absence of the necessary cis-acting sequences. Finally, the EBOV protein VP30 was identified as a trans-acting factor for RNA editing, constituting a novel function for this protein. Overall, our results provide novel insights into the RNA editing mechanism of EBOV, further understanding of which might result in novel intervention strategies against this viral pathogen. |
| format |
article |
| author |
Masfique Mehedi Thomas Hoenen Shelly Robertson Stacy Ricklefs Michael A Dolan Travis Taylor Darryl Falzarano Hideki Ebihara Stephen F Porcella Heinz Feldmann |
| author_facet |
Masfique Mehedi Thomas Hoenen Shelly Robertson Stacy Ricklefs Michael A Dolan Travis Taylor Darryl Falzarano Hideki Ebihara Stephen F Porcella Heinz Feldmann |
| author_sort |
Masfique Mehedi |
| title |
Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. |
| title_short |
Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. |
| title_full |
Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. |
| title_fullStr |
Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. |
| title_full_unstemmed |
Ebola virus RNA editing depends on the primary editing site sequence and an upstream secondary structure. |
| title_sort |
ebola virus rna editing depends on the primary editing site sequence and an upstream secondary structure. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/9a86172cb41f4c639f27d3a149d1d0d4 |
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