UMMS Affiliation

Program in Molecular Medicine; Department of Molecular Genetics and Microbiology

Publication Date

8-1-1992

Document Type

Article

Subjects

Animals; Base Sequence; Blotting, Western; *Gene Expression Regulation, Viral; Introns; Macaca mulatta; Molecular Sequence Data; Nucleic Acid Conformation; Oligodeoxyribonucleotides; Plasmids; *Protein Biosynthesis; *RNA Splicing; RNA, Messenger; RNA, Viral; Simian immunodeficiency virus; Transcription, Genetic

Disciplines

Immunology and Infectious Disease | Microbiology | Molecular Genetics | Virology

Abstract

The untranslated leader sequences of rhesus macaque simian immunodeficiency virus mRNAs form a stable secondary structure, TAR. This structure can be modified by RNA splicing. In this study, the role of TAR splicing in virus replication was investigated. The proportion of viral RNAs containing a spliced TAR structure is high early after infection and decreases at later times. Moreover, proviruses containing mutations which prevent TAR splicing are significantly delayed in replication. These mutant viruses require approximately 20 days to achieve half-maximal virus production, in contrast to wild-type viruses, which require approximately 8 days. We attribute this delay to the inefficient translation of unspliced-TAR-containing mRNAs. The molecular basis for this translational effect was examined in in vitro assays. We found that spliced-TAR-containing mRNAs were translated up to 8.5 times more efficiently than were similar mRNAs containing an unspliced TAR leader. Furthermore, these spliced-TAR-containing mRNAs were more efficiently associated with ribosomes. We postulate that the level of TAR splicing provides a balance for the optimal expression of both viral proteins and genomic RNA and therefore ultimately controls the production of infectious virions.

Comments

Citation: J Virol. 1992 Aug;66(8):4824-33. Link to article on publisher's site

Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of virology

PubMed ID

1629957

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