Conformational flexibility in the enterovirus RNA replication platform

RNA. 2019 Mar;25(3):376-387. doi: 10.1261/rna.069476.118. Epub 2018 Dec 21.

Abstract

A presumed RNA cloverleaf (5'CL), located at the 5'-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem-loop B (SLB) and stem-loop D (SLD), the two largest stem-loops within the 5'CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5'CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB and SLD into close contact, a geometry that creates an extensive accessible major groove surface, and permits interaction between the proteins that target each stem-loop.

Keywords: NMR; RNA; SAXS; cloverleaf; enterovirus; replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Enterovirus / genetics*
  • Gene Expression Regulation, Viral
  • Magnesium / chemistry
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Nucleic Acid Conformation*
  • RNA, Viral / chemistry*
  • RNA, Viral / genetics*
  • Structure-Activity Relationship
  • Transcription, Genetic*
  • Virus Replication

Substances

  • RNA, Viral
  • Magnesium