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Ribosomal S27a coding sequences upstream of ubiquitin coding sequences in the genome of a pestivirus.

ABSTRACT: Molecular characterization of cytopathogenic (cp) bovine viral diarrhea virus (BVDV) strain CP Rit, a temperature-sensitive strain widely used for vaccination, revealed that the viral genomic RNA is about 15.2 kb long, which is about 2.9 kb longer than the one of noncytopathogenic (noncp) BVDV strains. Molecular cloning and nucleotide sequencing of parts of the genome resulted in the identification of a duplication of the genomic region encoding nonstructural proteins NS3, NS4A, and part of NS4B. In addition, a nonviral sequence was found directly upstream of the second copy of the NS3 gene. The 3' part of this inserted sequence encodes an N-terminally truncated ubiquitin monomer. This is remarkable since all described cp BVDV strains with ubiquitin coding sequences contain at least one complete ubiquitin monomer. The 5' region of the nonviral sequence did not show any homology to cellular sequences identified thus far in cp BVDV strains. Databank searches revealed that this second cellular insertion encodes part of ribosomal protein S27a. Further analyses included molecular cloning and nucleotide sequencing of the cellular recombination partner. Sequence comparisons strongly suggest that the S27a and the ubiquitin coding sequences found in the genome of CP Rit were both derived from a bovine mRNA encoding a hybrid protein with the structure NH2-ubiquitin-S27a-COOH. Polyprotein processing in the genomic region encoding the N-terminal part of NS4B, the two cellular insertions, and NS3 was studied by a transient-expression assay. The respective analyses showed that the S27a-derived polypeptide, together with the truncated ubiquitin, served as processing signal to yield NS3, whereas the truncated ubiquitin alone was not capable of mediating the cleavage. Since the expression of NS3 is strictly correlated with the cp phenotype of BVDV, the altered genome organization leading to expression of NS3 most probably represents the genetic basis of cytopathogenicity of CP Rit.

SUBMITTER: Becher P

PROVIDER: S-EPMC110283 | biostudies-literature | 1998 Nov

REPOSITORIES: biostudies-literature

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Ribosomal S27a coding sequences upstream of ubiquitin coding sequences in the genome of a pestivirus.

Becher P P Orlich M M Thiel H J HJ

Journal of virology 19981101 11

Molecular characterization of cytopathogenic (cp) bovine viral diarrhea virus (BVDV) strain CP Rit, a temperature-sensitive strain widely used for vaccination, revealed that the viral genomic RNA is about 15.2 kb long, which is about 2.9 kb longer than the one of noncytopathogenic (noncp) BVDV strains. Molecular cloning and nucleotide sequencing of parts of the genome resulted in the identification of a duplication of the genomic region encoding nonstructural proteins NS3, NS4A, and part of NS4B ...[more]

PMID: 9765411

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Project description:Upstream open reading frames (uORFs) are translational regulatory elements located in 5' untranslated regions. They can significantly repress the translation of the downstream coding sequences (CDS), and participate in the spatio-temporal regulations of protein translation. Notwithstanding this biological significance, the selective constraint on uORFs remains underexplored. Particularly, the uORFs that partially overlap with CDS with a different reading frame (overlapping uORFs, or "VuORFs") may lead to strong translational inhibition or N-terminal truncation of the peptides encoded by the affected CDS. By analyzing VuORF-containing transcripts (designated as "VuORF transcripts") in human, mouse, and fruit fly, we demonstrate that VuORFs are in general slightly deleterious--the proportion of genes that encode at least one VuORF transcript is significantly smaller than expected in all of the three examined species. In addition, this proportion is significantly smaller in fruit fly than in mammals, indicating a higher efficiency of removing VuORFs in the former species because of its larger effective population size. Furthermore, the deleterious effect of a VuORF depends on the sequence context of its start codon (VuAUG). VuORFs with an optimal VuAUG context are more strongly disfavored than those with a suboptimal context in all of the three examined species. And the propensity to remove optimal-context VuAUGs is stronger in fruit fly than in mammals. Intriguingly, however, the currently observable optimal-context VuAUGs (but not suboptimal-context VuAUGs) are more conserved than expected. These observations suggest that the regulatory functions of VuORFs may have been gained fortuitously in organisms with a small effective population size because the slightly deleterious effect of these elements can be better tolerated in these organisms, thus allowing opportunities for the development of novel biological functions. Nevertheless, once the functions of VuORFs were established, they became subject to negative selection.

Dataset Information

Ribosomal S27a coding sequences upstream of ubiquitin coding sequences in the genome of a pestivirus.

Publications

Ribosomal S27a coding sequences upstream of ubiquitin coding sequences in the genome of a pestivirus.

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