Nucleic Acids Research, 2001, Vol. 29, No. 12 2535-2541
© 2001 Oxford University Press
Hepatitis C virus internal ribosome entry site RNA contains a tertiary structural element in a functional domain of stem–loop II
Program in Biochemistry and Structural Biology, Weill Graduate School of Medical Sciences of Cornell University, 1300 York Avenue, New York, NY 10021, USA and 1Laboratorio Hepatologia-Medicina Interna, Edificio Almacenes Generales, Hospital del Valle d’Hebron, Paseo del Valle de Hebron s/n 08035, Barcelona, Spain
The internal ribosome entry site (IRES) of hepatitis C virus (HCV) RNA contains >300 bases of highly conserved 5'-terminal sequence, most of it in the uncapped 5'-untranslated region (5'-UTR) upstream from the single AUG initiator triplet at which translation of the HCV polyprotein begins. Although progress has been made in defining singularities like the RNA pseudoknot near this AUG, the sequence and structural features of the HCV IRES which stimulate accurate and efficient initiation of protein synthesis are only partially defined. Here we report that a region further upstream from the AUG, stem–loop II of the HCV IRES, also contains an element of local tertiary structure which we have detected using RNase H cleavage and have mapped using the singular ability of two bases therein to undergo covalent intra-chain crosslinking stimulated by UV light. This pre-existing element maps to two non-contiguous stretches of the HCV IRES sequence, residues 53–68 and 103–117. Several earlier studies have shown that the correct sequence between bases 45 and 70 of the HCV IRES stem–loop II domain is required for initiation of protein synthesis. Because features of local tertiary structure like the one we report here are often associated with protein binding, we propose that the HCV stem–loop II element is directly involved in IRES action.
* To whom correspondence should be addressed. Tel: +1 212 746 6400; Fax: +1 212 746 8144; Email: hdrober{at}mail.med.cornell.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Diaz-Toledano, A. Ariza-Mateos, A. Birk, B. Martinez-Garcia, and J. Gomez In vitro characterization of a miR-122-sensitive double-helical switch element in the 5' region of hepatitis C virus RNA Nucleic Acids Res., July 3, 2009; (2009) gkp553v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Baird, M. Turcotte, R. G. Korneluk, and M. Holcik Searching for IRES RNA, October 1, 2006; 12(10): 1755 - 1785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. FERNANDEZ-MIRAGALL, R. RAMOS, J. RAMAJO, and E. MARTINEZ-SALAS Evidence of reciprocal tertiary interactions between conserved motifs involved in organizing RNA structure essential for internal initiation of translation RNA, February 1, 2006; 12(2): 223 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Beguiristain, H. D. Robertson, and J. Gomez RNase III cleavage demonstrates a long range RNA: RNA duplex element flanking the hepatitis C virus internal ribosome entry site Nucleic Acids Res., September 16, 2005; 33(16): 5250 - 5261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Piron, N. Beguiristain, A. Nadal, E. Martinez-Salas, and J. Gomez Characterizing the function and structural organization of the 5' tRNA-like motif within the hepatitis C virus quasispecies Nucleic Acids Res., March 8, 2005; 33(5): 1487 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Martineau, C. Le Bec, L. Monbrun, V. Allo, I.-M. Chiu, O. Danos, H. Moine, H. Prats, and A.-C. Prats Internal Ribosome Entry Site Structural Motifs Conserved among Mammalian Fibroblast Growth Factor 1 Alternatively Spliced mRNAs Mol. Cell. Biol., September 1, 2004; 24(17): 7622 - 7635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Martell, C. Briones, A. de Vicente, M. Piron, J. I. Esteban, R. Esteban, J. Guardia, and J. Gomez Structural analysis of hepatitis C RNA genome using DNA microarrays Nucleic Acids Res., June 24, 2004; 32(11): e90 - e90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Lyons and H. D. Robertson Detection of tRNA-like Structure through RNase P Cleavage of Viral Internal Ribosome Entry Site RNAs Near the AUG Start Triplet J. Biol. Chem., July 11, 2003; 278(29): 26844 - 26850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. VYAS, A. ELIA, and M. J. CLEMENS Inhibition of the protein kinase PKR by the internal ribosome entry site of hepatitis C virus genomic RNA RNA, July 1, 2003; 9(7): 858 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nadal, H. D. Robertson, J. Guardia, and J. Gomez Characterization of the structure and variability of an internal region of hepatitis C virus RNA for M1 RNA guide sequence ribozyme targeting J. Gen. Virol., June 1, 2003; 84(6): 1545 - 1548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A CIRCLE, A. J. LYONS, O. D. NEEL, and H. D. ROBERTSON Recurring features of local tertiary structural elements in RNA molecules exemplified by hepatitis D virus RNA RNA, March 1, 2003; 9(3): 280 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nadal, M. Martell, J. R. Lytle, A. J. Lyons, H. D. Robertson, B. Cabot, J. I. Esteban, R. Esteban, J. Guardia, and J. Gomez Specific Cleavage of Hepatitis C Virus RNA Genome by Human RNase P J. Biol. Chem., August 16, 2002; 277(34): 30606 - 30613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lafuente, R. Ramos, and E. Martinez-Salas Long-range RNA-RNA interactions between distant regions of the hepatitis C virus internal ribosome entry site element J. Gen. Virol., May 1, 2002; 83(5): 1113 - 1121. [Abstract] [Full Text] [PDF]
|
|