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RNA Structure Modulates Splicing Efficiency at the Human Immunodeficiency Virus Type 1 Major Splice Donor

Overview
Journal J Virol
Date 2007 Dec 28
PMID 18160437
Citations 54
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Abstract

The untranslated leader of the human immunodeficiency virus type 1 (HIV-1) RNA genome encodes essential sequence and structural motifs that control various replication steps. The 5' splice site or splice donor (SD) is embedded in a semistable hairpin, but the function of this structure is unknown. We stabilized this SD hairpin by creating an additional base pair and demonstrated a severe HIV-1 replication defect. A splicing defect was apparent in RNA analyses of virus-infected cells and cells transfected with appropriate reporter constructs. We selected multiple virus revertants in search for interesting second-site escape pathways. Most revertants acquired an additional mutation that modulated the stability of the mutant SD hairpin. One revertant acquired a single nucleotide change in the upstream DIS hairpin. We demonstrate that a novel SD site is created by this upstream mutation, which obviously reduces the number of leader nucleotides that are included in spliced HIV-1 transcripts. These results suggest a novel role of RNA structure in the regulation of HIV-1 splicing.

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References
1.
Klaver B, Berkhout B . Evolution of a disrupted TAR RNA hairpin structure in the HIV-1 virus. EMBO J. 1994; 13(11):2650-9. PMC: 395139. DOI: 10.1002/j.1460-2075.1994.tb06555.x. View

2.
Klaver B, Berkhout B . Comparison of 5' and 3' long terminal repeat promoter function in human immunodeficiency virus. J Virol. 1994; 68(6):3830-40. PMC: 236888. DOI: 10.1128/JVI.68.6.3830-3840.1994. View

3.
Jacquenet S, Ropers D, Bilodeau P, Damier L, Mougin A, Stoltzfus C . Conserved stem-loop structures in the HIV-1 RNA region containing the A3 3' splice site and its cis-regulatory element: possible involvement in RNA splicing. Nucleic Acids Res. 2001; 29(2):464-78. PMC: 29680. DOI: 10.1093/nar/29.2.464. View

4.
Huthoff H, Berkhout B . Two alternating structures of the HIV-1 leader RNA. RNA. 2001; 7(1):143-57. PMC: 1370064. DOI: 10.1017/s1355838201001881. View

5.
Berkhout B, Das A, Beerens N . HIV-1 RNA editing, hypermutation, and error-prone reverse transcription. Science. 2001; 292(5514):7. DOI: 10.1126/science.292.5514.7a. View