Grewe, Bastian and Vogt, Carolin and Horstkoetter, Theresa and Tippler, Bettina and Xiao, Han and Mueller, Bianca and Ueberla, Klaus and Wagner, Ralf and Asbach, Benedikt and Bohne, Jens (2021) The HIV 5 ' Gag Region Displays a Specific Nucleotide Bias Regulating Viral Splicing and Infectivity. VIRUSES-BASEL, 13 (6): 997. ISSN , 1999-4915
Full text not available from this repository. (Request a copy)Abstract
Alternative splicing and the expression of intron-containing mRNAs is one hallmark of HIV gene expression. To facilitate the otherwise hampered nuclear export of non-fully processed mRNAs, HIV encodes the Rev protein, which recognizes its intronic response element and fuels the HIV RNAs into the CRM-1-dependent nuclear protein export pathway. Both alternative splicing and Rev-dependency are regulated by the primary HIV RNA sequence. Here, we show that these processes are extremely sensitive to sequence alterations in the 5'coding region of the HIV genomic RNA. Increasing the GC content by insertion of either GFP or silent mutations activates a cryptic splice donor site in gag, entirely deregulates the viral splicing pattern, and lowers infectivity. Interestingly, an adaptation of the inserted GFP sequence toward an HIV-like nucleotide bias reversed these phenotypes completely. Of note, the adaptation yielded completely different primary sequences although encoding the same amino acids. Thus, the phenotypes solely depend on the nucleotide composition of the two GFP versions. This is a strong indication of an HIV-specific mRNP code in the 5 ' gag region wherein the primary RNA sequence bias creates motifs for RNA-binding proteins and controls the fate of the HIV-RNA in terms of viral gene expression and infectivity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESSENGER-RNA; VIRUS RNA; SEQUENCE; REPLICATION; ACTIVATION; EXPRESSION; STABILITY; PROTEINS; ELEMENTS; SR; HIV gene expression; U1 snRNP; mRNP code; alternative splicing |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Sep 2022 13:22 |
| Last Modified: | 09 Sep 2022 13:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46953 |
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