Abstract:
:The viral RNA (vRNA) genome of influenza viruses is replicated by the RNA-dependent RNA polymerase (RNAP) via a complementary RNA (cRNA) intermediate. The vRNA promoter can adopt multiple conformations when bound by the RNAP. However, the dynamics, determinants, and biological role of these conformations are unknown; further, little is known about cRNA promoter conformations. To probe the RNA conformations adopted during initial replication, we monitored single, surface-immobilized vRNA and cRNA initiation complexes in real-time. Our results show that, while the 3' terminus of the vRNA promoter exists in dynamic equilibrium between pre-initiation and initiation conformations, the cRNA promoter exhibited very limited dynamics. Two residues in the proximal 3' region of the cRNA promoter (residues absent in the vRNA promoter) allowed the cRNA template strand to reach further into the active site, limiting promoter dynamics. Our results highlight promoter-dependent differences in influenza initiation mechanisms, and advance our understanding of virus replication.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Robb NC,Te Velthuis AJW,Fodor E,Kapanidis ANdoi
10.1093/nar/gkz313subject
Has Abstractpub_date
2019-07-09 00:00:00pages
6466-6477issue
12eissn
0305-1048issn
1362-4962pii
5481152journal_volume
47pub_type
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