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The HIV-1 Tat Protein Enhances Splicing at the Major Splice Donor Site. | LitMetric

The HIV-1 Tat Protein Enhances Splicing at the Major Splice Donor Site.

J Virol

Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Published: July 2018

AI Article Synopsis

  • * The viral Tat protein is crucial in this process, as it not only activates transcription but also stimulates splicing at the major splice donor site, linking these two essential functions tightly together.
  • * Proper regulation of splicing is vital for optimal HIV-1 replication, as differentially spliced mRNAs are necessary for producing various viral proteins, emphasizing the importance of the Tat protein in maintaining this balance.

Article Abstract

Transcription of the HIV-1 proviral DNA and subsequent processing of the primary transcript results in the production of a large set of unspliced and differentially spliced viral RNAs. The major splice donor site (5'ss) that is located in the untranslated leader of the HIV-1 transcript is used for the production of all spliced RNAs, and splicing at this site has to be tightly regulated to allow the balanced production of all viral RNAs and proteins. We demonstrate that the viral Tat protein, which is known to activate viral transcription, also stimulates splicing at the major 5'ss. As for the transcription effect, Tat requires the viral long terminal repeat promoter and the -acting responsive RNA hairpin for splicing regulation. These results indicate that HIV-1 transcription and splicing are tightly coupled processes through the coordinated action of the essential Tat protein. The HIV-1 proviral DNA encodes a single RNA transcript that is used as RNA genome and packaged into newly assembled virus particles. This full-length RNA is also used as mRNA for the production of structural and enzymatic proteins. Production of other essential viral proteins depends on alternative splicing of the primary transcript, which yields a large set of differentially spliced mRNAs. Optimal virus replication requires a balanced production of all viral RNAs, which means that the splicing process has to be strictly regulated. We show that the HIV-1 Tat protein, a factor that is well known for its transcription activating function, also stimulates splicing. Thus, Tat controls not only the level of the viral RNA but also the balance between spliced and unspliced RNAs.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026763PMC
http://dx.doi.org/10.1128/JVI.01855-17DOI Listing

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