A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2016 Jul 26

PMID 27455303

Citations 5

Authors

Nancy Mueller

Atze T Das

Ben Berkhout

Affiliations

Soon will be listed here.

Abstract

RNA splicing is a critical step in the human immunodeficiency virus type 1 (HIV-1) replication cycle because it controls the expression of the complex viral proteome. The major 5' splice site (5'ss) that is positioned in the untranslated leader of the HIV-1 RNA transcript is of particular interest because it is used for the production of the more than 40 differentially spliced subgenomic mRNAs. HIV-1 splicing needs to be balanced tightly to ensure the proper levels of all viral proteins, including the Gag-Pol proteins that are translated from the unspliced RNA. We previously presented evidence that the major 5'ss is regulated by a repressive local RNA structure, the splice donor (SD) hairpin, that masks the 11 nucleotides (nts) of the 5'ss signal for recognition by U1 small nuclear RNA (snRNA) of the spliceosome machinery. A strikingly different multiple-hairpin RNA conformation was recently proposed for this part of the HIV-1 leader RNA. We therefore inspected the sequence of natural HIV-1 isolates in search for support, in the form of base pair (bp) co-variations, for the different RNA conformations.

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References

Amarasinghe G, De Guzman R, Turner R, Summers M . NMR structure of stem-loop SL2 of the HIV-1 psi RNA packaging signal reveals a novel A-U-A base-triple platform. J Mol Biol. 2000; 299(1):145-56. DOI: 10.1006/jmbi.2000.3710. View

Mueller N, Berkhout B, Das A . HIV-1 splicing is controlled by local RNA structure and binding of splicing regulatory proteins at the major 5' splice site. J Gen Virol. 2015; 96(Pt 7):1906-17. DOI: 10.1099/vir.0.000122. View

Goguel V, Wang Y, Rosbash M . Short artificial hairpins sequester splicing signals and inhibit yeast pre-mRNA splicing. Mol Cell Biol. 1993; 13(11):6841-8. PMC: 364746. DOI: 10.1128/mcb.13.11.6841-6848.1993. View

Berkhout B . Structural features in TAR RNA of human and simian immunodeficiency viruses: a phylogenetic analysis. Nucleic Acids Res. 1992; 20(1):27-31. PMC: 310321. DOI: 10.1093/nar/20.1.27. View

Sakaguchi K, Zambrano N, Baldwin E, Shapiro B, Erickson J, Omichinski J . Identification of a binding site for the human immunodeficiency virus type 1 nucleocapsid protein. Proc Natl Acad Sci U S A. 1993; 90(11):5219-23. PMC: 46687. DOI: 10.1073/pnas.90.11.5219. View

Michel F, Jacquier A, Dujon B . Comparison of fungal mitochondrial introns reveals extensive homologies in RNA secondary structure. Biochimie. 1982; 64(10):867-81. DOI: 10.1016/s0300-9084(82)80349-0. View

Singh N, Singh R, Androphy E . Modulating role of RNA structure in alternative splicing of a critical exon in the spinal muscular atrophy genes. Nucleic Acids Res. 2006; 35(2):371-89. PMC: 1802598. DOI: 10.1093/nar/gkl1050. View

Pappalardo L, Kerwood D, Pelczer I, Borer P . Three-dimensional folding of an RNA hairpin required for packaging HIV-1. J Mol Biol. 1998; 282(4):801-18. DOI: 10.1006/jmbi.1998.2046. View

Asang C, Erkelenz S, Schaal H . The HIV-1 major splice donor D1 is activated by splicing enhancer elements within the leader region and the p17-inhibitory sequence. Virology. 2012; 432(1):133-45. DOI: 10.1016/j.virol.2012.06.004. View

10.

Buratti E, Baralle F . Influence of RNA secondary structure on the pre-mRNA splicing process. Mol Cell Biol. 2004; 24(24):10505-14. PMC: 533984. DOI: 10.1128/MCB.24.24.10505-10514.2004. View

11.

Klasens B, Das A, Berkhout B . Inhibition of polyadenylation by stable RNA secondary structure. Nucleic Acids Res. 1998; 26(8):1870-6. PMC: 147501. DOI: 10.1093/nar/26.8.1870. View

12.

Clever J, Sassetti C, Parslow T . RNA secondary structure and binding sites for gag gene products in the 5' packaging signal of human immunodeficiency virus type 1. J Virol. 1995; 69(4):2101-9. PMC: 188876. DOI: 10.1128/JVI.69.4.2101-2109.1995. View

13.

van Bel N, Ghabri A, Das A, Berkhout B . The HIV-1 leader RNA is exquisitely sensitive to structural changes. Virology. 2015; 483:236-52. DOI: 10.1016/j.virol.2015.03.050. View

14.

Harrison G, Miele G, Hunter E, Lever A . Functional analysis of the core human immunodeficiency virus type 1 packaging signal in a permissive cell line. J Virol. 1998; 72(7):5886-96. PMC: 110392. DOI: 10.1128/JVI.72.7.5886-5896.1998. View

15.

Mueller N, van Bel N, Berkhout B, Das A . HIV-1 splicing at the major splice donor site is restricted by RNA structure. Virology. 2014; 468-470:609-620. DOI: 10.1016/j.virol.2014.09.018. View

16.

Abbink T, Berkhout B . RNA structure modulates splicing efficiency at the human immunodeficiency virus type 1 major splice donor. J Virol. 2007; 82(6):3090-8. PMC: 2258995. DOI: 10.1128/JVI.01479-07. View

17.

Warf M, Berglund J . Role of RNA structure in regulating pre-mRNA splicing. Trends Biochem Sci. 2009; 35(3):169-78. PMC: 2834840. DOI: 10.1016/j.tibs.2009.10.004. View

18.

Spillantini M, Murrell J, Goedert M, Farlow M, Klug A, Ghetti B . Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc Natl Acad Sci U S A. 1998; 95(13):7737-41. PMC: 22742. DOI: 10.1073/pnas.95.13.7737. View

19.

Shepard P, Hertel K . Conserved RNA secondary structures promote alternative splicing. RNA. 2008; 14(8):1463-9. PMC: 2491482. DOI: 10.1261/rna.1069408. View

20.

Grover A, Houlden H, Baker M, Adamson J, Lewis J, Prihar G . 5' splice site mutations in tau associated with the inherited dementia FTDP-17 affect a stem-loop structure that regulates alternative splicing of exon 10. J Biol Chem. 1999; 274(21):15134-43. DOI: 10.1074/jbc.274.21.15134. View