This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.02622-07v1 82/8/3882    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Moreno, J. L. Articles by Sola, I. PubMed PubMed Citation Articles by Moreno, J. L. Articles by Sola, I.

 Previous Article  |  Next Article 

Journal of Virology, April 2008, p. 3882-3893, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.02622-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of a Coronavirus Transcription Enhancer

Centro Nacional de Biotecnología, CSIC, Department of Molecular and Cell Biology, C/Darwin 3, Cantoblanco, 28049 Madrid, Spain

Received 10 December 2007/ Accepted 1 February 2008

Coronavirus (CoV) transcription includes a discontinuous mechanism during the synthesis of sub-genome-length minus-strand RNAs leading to a collection of mRNAs in which the 5' terminal leader sequence is fused to contiguous genome sequences. It has been previously shown that transcription-regulating sequences (TRSs) preceding each gene regulate transcription. Base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) in the nascent RNA is a determinant factor during CoV transcription. In fact, in transmissible gastroenteritis CoV, a good correlation has been observed between subgenomic mRNA (sg mRNA) levels and the free energy (G) of TRS-L and cTRS-B duplex formation. The only exception was sg mRNA N, the most abundant sg mRNA during viral infection in spite of its minimum G associated with duplex formation. We postulated that additional factors should regulate transcription of sg mRNA N. In this report, we have described a novel transcription regulation mechanism operating in CoV by which a 9-nucleotide (nt) sequence located 449 nt upstream of the N gene TRS core sequence (CS-N) interacts with a complementary sequence just upstream of CS-N, specifically increasing the accumulation of sg mRNA N. Alteration of this complementarity in mutant replicon genomes showed a correlation between the predicted stability of the base pairing between 9-nt sequences and the accumulation of sg mRNA N. This interaction is exclusively conserved in group 1a CoVs, the only CoV subgroup in which the N gene is not the most 3' gene in the viral genome. This is the first time that a long-distance RNA-RNA interaction regulating transcriptional activity specifically enhancing the transcription of one gene has been described to occur in CoVs.

Published ahead of print on 13 February 2008.