title: Oscillating kissing stem-loop interactions mediate 5' scanning-dependent translation by a viral 3'-cap-independent translation element.
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.
authors.affiliation: Molecular, Cellular, and Developmental Biology Program and Plant Pathology Department, Iowa State University, Ames, Iowa 50011, USA.
authors.forename: Aurélie M
authors.initials: AM
authors.lastname: Rakotondrafara
authors.forename: Charlotta
authors.initials: C
authors.lastname: Polacek
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
authors.forename: W Allen
authors.initials: WA
authors.lastname: Miller
mesh_terms: D020413:3' Untranslated Regions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020121:5' Untranslated Regions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D003716:Dengue Virus / Q000235:genetics / Q000378:metabolism; D017793:Luteovirus / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D012315:RNA Caps; D012367:RNA, Viral