Fig. 5.

Model for the role of nsp14 in proofreading and mRNA capping. Nascent RNA is synthesized at the polymerization sites (red circle) of the nsp12 RdRp domain (gray) or is mismatch excised at the proofreading site (red circles) of nsp14 ExoN (green surface). The relative orientation of the polymerization and proofreading domains is built based on the Klenow fragment. The 5′ end of newly synthesized mRNA is modified by sequential activities contributed by RTPase of nsp13, GTase (currently unknown), N7-MTase of nsp14, and 2′-O–MTase of nsp16 (light pink surface, PDB ID code 3R24) for formation of a cap1 structure.