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Published September 1, 1982 | Published
Journal Article Open

Sequence Studies of Several Alphavirus Genomic RNAs in the Region Containing the Start of the Subgenomic RNA


The alphaviruses produce two mRNAs after infection: the genomic (49S) RNA which is translated into the nonstructural (replicase) proteins and the subgenomic (26S) RNA which serves as the mRNA for the virion structural proteins. The sequence of the region of the genomic RNA that contains the 5' end of the subgenomic RNA and the 5' flanking sequences in the genomic RNA were determined for several alphaviruses. A highly conserved sequence of 21 nucleotides was found which includes the first two nucleotides of the subgenomic RNA and the 19 nucleotides preceding it. We propose that the complement of this sequence in the minus strand is the recognition site used by the viral transcriptase for initiation of transcription of 26S RNA and that, in general, such short recognition sequences are commonly used among the RNA viruses. The COOH-terminal sequence of the nonstructural polyprotein precursor has been deduced for each virus. These protein sequences are highly homologous and are followed by multiple in-phase termination codons clustered in the nontranslated region of the 26S RNA in each case. In contrast to the proposed transcriptase recognition site, the particular triplets used for a given conserved amino acid have diverged markedly during evolution of these viruses. The protein homology is sufficient, however, for deduction of the correct coding phase of the RNA and allows the alignment of the corresponding nucleic acid sequence data from different alphaviruses without knowledge of the sequence of the entire genomes.

Additional Information

Copyright © 1982 by the National Academy of Sciences. Communicated by Ray D. Owen, June 7, 1982. Note Added in Proof. The sequence of the junction region of Semliki Forest virus has been determined recently (24). Our results are in agreement with those reported, with five nucleotide changes, probably due to strain differences, in the region analyzed. We are grateful to Mrs. E.M. Lenches for preparing chicken embryo cell cultures, to T. Hunkapiller for assistance with the computer work, and to J.R. Bell for critical discussion of the manuscript. This work was supported by Grants PCM 8022830 from the National Science Foundation, GM 06965 and AI 10793 from the National Institutes of Health, and Biomedical Research Support Grant 507RR 07003 from the National Institutes of Health. J.O. was supported in part by Training Grant GM 00086 from the National Institutes of Health; C. M.R. was supported by a fellowship from the Gosney Foundation. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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