@article{179521,
  author = {Aartjan Te Velthuis and Nicole Robb and Achillefs Kapanidis and Ervin Fodor},
  title = {The role of the priming loop in  RNA synthesis},
  abstract = { RNA-dependent RNA polymerases (RdRps) are used by RNA viruses to replicate and transcribe their RNA genomes1. They adopt a closed, right-handed fold with conserved subdomains called palm, fingers, and thumb1,2. Conserved RdRp motifs A-F coordinate the viral RNA template, NTPs, and magnesium ions to facilitate nucleotide condensation1. For the initiation of RNA synthesis, most RdRps use either a primer-dependent or  mechanism3. The  RdRp in contrast, uses a capped RNA oligonucleotide to initiate transcription, and a combination of terminal and internal  initiation for replication4. To understand how the  RdRp coordinates these processes, we analysed the function of a thumb subdomain β-hairpin using initiation, elongation, and single-molecule FRET assays. Our data shows that this β-hairpin is essential for terminal initiation during replication, but auxiliary for internal initiation and transcription. Analysis of individual residues in the tip of the β-hairpin shows that PB1 proline 651 is critical for efficient RNA synthesis  and in cell culture. Overall, this work advances our understanding of  RNA synthesis and identifies the initiation platform of viral replication. },
  year = {2016},
  journal = {Nat Microbiol},
  volume = {1},
  month = {05/2016},
  issn = {2058-5276},
  doi = {10.1038/nmicrobiol.2016.29},
  language = {eng},
}