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

DOI: 10.1093/nar/gky637 DOI Help

Authors: Baptiste Martin (AFMB, CNRS, Aix-Marseille Universite) , Bruno Coutard (AFMB, CNRS, Aix-Marseille Universite) , Théo Guez (IBMM, University of Montpellier) , Guido C. Paesen (Wellcome Centre for Human Genetics, University of Oxford) , Bruno Canard (AFMB, CNRS, Aix-Marseille Universite) , Françoise Debart (IBMM, University of Montpellier) , Jean-Jacques Vasseur (IBMM, University of Montpellier) , Jonathan M. Grimes (Wellcome Centre for Human Genetics, University of Oxford, University of Oxford; Diamond Light Source) , Etienne Decroly (AFMB, CNRS, Aix-Marseille Universite)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nucleic Acids Research , VOL 46 , PAGES 7902 - 7912

State: Published (Approved)
Published: September 2018

Open Access Open Access

Abstract: Mononegaviruses, such as Ebola virus, encode an L (large) protein that bears all the catalytic activities for replication/transcription and RNA capping. The C-terminal conserved region VI (CRVI) of L protein contains a K-D-K-E catalytic tetrad typical for 2’O methyltransferases (MTase). In mononegaviruses, cap-MTase activities have been involved in the 2’O methylation and N7 methylation of the RNA cap structure. These activities play a critical role in the viral life cycle as N7 methylation ensures efficient viral mRNA translation and 2’O methylation hampers the detection of viral RNA by the host innate immunity. The functional characterization of the MTase+CTD domain of Sudan ebolavirus (SUDV) revealed cap-independent methyltransferase activities targeting internal adenosine residues. Besides this, the MTase+CTD also methylates, the N7 position of the cap guanosine and the 2’O position of the n1 guanosine provided that the RNA is sufficiently long. Altogether, these results suggest that the filovirus MTases evolved towards a dual activity with distinct substrate specificities. Whereas it has been well established that cap-dependent methylations promote protein translation and help to mimic host RNA, the characterization of an original cap-independent methylation opens new research opportunities to elucidate the role of RNA internal methylations in the viral replication.

Diamond Keywords: Ebola; Viruses

Subject Areas: Biology and Bio-materials, Chemistry

Technical Areas:

Added On: 10/09/2018 12:14

Discipline Tags:

Pathogens Infectious Diseases Disease in the Developing World Health & Wellbeing Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags: