Oscillating kissing stem-loop interactions mediate 5' scanning-dependent translation by a viral 3'-cap-independent translation element

RNA. 2006 Oct;12(10):1893-906. doi: 10.1261/rna.115606. Epub 2006 Aug 18.

Abstract

The 3'-untranslated regions (UTRs) of a group of novel uncapped viral RNAs allow efficient translation initiation at the 5'-proximal AUG. A well-characterized model is the Barley yellow dwarf virus class of cap-independent translation elements (BTE). It facilitates translation by forming kissing stem-loops between the BTE in the 3'-UTR and a BTE-complementary loop in the 5'-UTR. Here we investigate the mechanisms of the long-distance interaction and ribosome entry on the RNA. Upstream AUGs or 5'-extensions of the 5'-UTR inhibit translation, indicating that, unlike internal ribosome entry sites in many viral RNAs, the BTE relies on 5'-end-dependent ribosome scanning. Cap-independent translation occurs when the kissing sites are moved to different regions in either UTR, including outside of the BTE. The BTE can even confer cap-independent translation when fused to the 3'-UTR of a reporter RNA harboring dengue virus sequences that cause base-pairing between the 3'- and 5'-ends. Thus, the BTE serves as a functional sensor to detect sequences capable of long-distance base-pairing. We propose that the kissing interaction is repeatedly disrupted by the scanning ribosome and re-formed in an oscillating process that regulates ribosome entry on the RNA.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / chemistry
  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / metabolism
  • 5' Untranslated Regions / chemistry
  • 5' Untranslated Regions / genetics
  • 5' Untranslated Regions / metabolism
  • Base Sequence
  • Dengue Virus / genetics
  • Dengue Virus / metabolism
  • Luteovirus / genetics
  • Luteovirus / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Protein Biosynthesis
  • RNA Caps / chemistry
  • RNA Caps / genetics
  • RNA Caps / metabolism
  • RNA, Viral / chemistry*
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism
  • Ribosomes / metabolism

Substances

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • RNA Caps
  • RNA, Viral