New Way of Regulating Alternative Splicing in Retroviruses: the Promoter Makes a Difference

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2007 Jan 19

PMID 17229710

Citations 6

Authors

Jens Bohne

Axel Schambach

Daniela Zychlinski

Affiliations

Soon will be listed here.

Abstract

Alternative splicing has been recognized as a major mechanism for creating proteomic diversity from a limited number of genes. However, not all determinants regulating this process have been characterized. Using subviral human immunodeficiency virus (HIV) env constructs we observed an enhanced splicing of the RNA when expression was under control of the cytomegalovirus (CMV) promoter instead of the HIV long terminal repeat (LTR). We extended these observations to LTR- or CMV-driven murine leukemia proviruses, suggesting that retroviral LTRs are adapted to inefficient alternative splicing at most sites in order to maintain balanced gene expression.

Citing Articles

Cat and Mouse: HIV Transcription in Latency, Immune Evasion and Cure/Remission Strategies.

Delannoy A, Poirier M, Bell B Viruses. 2019; 11(3).

PMID: 30889861 PMC: 6466452. DOI: 10.3390/v11030269.

Beyond Transcription: Roles of Transcription Factors in Pre-mRNA Splicing.

Rambout X, Dequiedt F, Maquat L Chem Rev. 2017; 118(8):4339-4364.

PMID: 29251915 PMC: 6734189. DOI: 10.1021/acs.chemrev.7b00470.

Immunogenicity of a lentiviral-based DNA vaccine driven by the 5'LTR of the naturally attenuated caprine arthritis encephalitis virus (CAEV) in mice and macaques.

Arrode-Bruses G, Hegde R, Jin Y, Liu Z, Narayan O, Chebloune Y Vaccine. 2012; 30(19):2956-62.

PMID: 22387218 PMC: 3341415. DOI: 10.1016/j.vaccine.2012.02.050.

Limited complementarity between U1 snRNA and a retroviral 5' splice site permits its attenuation via RNA secondary structure.

Zychlinski D, Erkelenz S, Melhorn V, Baum C, Schaal H, Bohne J Nucleic Acids Res. 2009; 37(22):7429-40.

PMID: 19854941 PMC: 2794156. DOI: 10.1093/nar/gkp694.

The influenza A virus spliced messenger RNA M mRNA3 is not required for viral replication in tissue culture.

Jackson D, Lamb R J Gen Virol. 2008; 89(Pt 12):3097-3101.

PMID: 19008398 PMC: 4677827. DOI: 10.1099/vir.0.2008/004739-0.

References

Chang L, McNulty E, Martin M . Human immunodeficiency viruses containing heterologous enhancer/promoters are replication competent and exhibit different lymphocyte tropisms. J Virol. 1993; 67(2):743-52. PMC: 237426. DOI: 10.1128/JVI.67.2.743-752.1993. View

Robinson D, Elliott J, Chang L . Retroviral vector with a CMV-IE/HIV-TAR hybrid LTR gives high basal expression levels and is up-regulated by HIV-1 Tat. Gene Ther. 1995; 2(4):269-78. View

Tange T, Damgaard C, Guth S, Valcarcel J, Kjems J . The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer element. EMBO J. 2001; 20(20):5748-58. PMC: 125679. DOI: 10.1093/emboj/20.20.5748. View

Berro R, Kehn K, de la Fuente C, Pumfery A, Adair R, Wade J . Acetylated Tat regulates human immunodeficiency virus type 1 splicing through its interaction with the splicing regulator p32. J Virol. 2006; 80(7):3189-204. PMC: 1440361. DOI: 10.1128/JVI.80.7.3189-3204.2006. View

Roberts G, Gooding C, Mak H, Proudfoot N, Smith C . Co-transcriptional commitment to alternative splice site selection. Nucleic Acids Res. 1998; 26(24):5568-72. PMC: 148035. DOI: 10.1093/nar/26.24.5568. View

Goldstrohm A, Greenleaf A, Garcia-Blanco M . Co-transcriptional splicing of pre-messenger RNAs: considerations for the mechanism of alternative splicing. Gene. 2001; 277(1-2):31-47. DOI: 10.1016/s0378-1119(01)00695-3. View

Kraunus J, Schaumann D, Meyer J, Modlich U, Fehse B, Brandenburg G . Self-inactivating retroviral vectors with improved RNA processing. Gene Ther. 2004; 11(21):1568-78. DOI: 10.1038/sj.gt.3302309. View

Chang L, Zhang C . Infection and replication of Tat- human immunodeficiency viruses: genetic analyses of LTR and tat mutations in primary and long-term human lymphoid cells. Virology. 1995; 211(1):157-69. DOI: 10.1006/viro.1995.1388. View

Marchand V, Mereau A, Jacquenet S, Thomas D, Mougin A, Gattoni R . A Janus splicing regulatory element modulates HIV-1 tat and rev mRNA production by coordination of hnRNP A1 cooperative binding. J Mol Biol. 2002; 323(4):629-52. DOI: 10.1016/s0022-2836(02)00967-1. View

10.

Ott M, Schnolzer M, Garnica J, Fischle W, Emiliani S, Rackwitz H . Acetylation of the HIV-1 Tat protein by p300 is important for its transcriptional activity. Curr Biol. 1999; 9(24):1489-92. DOI: 10.1016/s0960-9822(00)80120-7. View

11.

Madsen J, Stoltzfus C . An exonic splicing silencer downstream of the 3' splice site A2 is required for efficient human immunodeficiency virus type 1 replication. J Virol. 2005; 79(16):10478-86. PMC: 1182660. DOI: 10.1128/JVI.79.16.10478-10486.2005. View

12.

Schambach A, Mueller D, Galla M, Verstegen M, Wagemaker G, Loew R . Overcoming promoter competition in packaging cells improves production of self-inactivating retroviral vectors. Gene Ther. 2006; 13(21):1524-33. DOI: 10.1038/sj.gt.3302807. View

13.

Purcell D, Martin M . Alternative splicing of human immunodeficiency virus type 1 mRNA modulates viral protein expression, replication, and infectivity. J Virol. 1993; 67(11):6365-78. PMC: 238071. DOI: 10.1128/JVI.67.11.6365-6378.1993. View

14.

Cook C, McNally M . Interaction between the negative regulator of splicing element and a 3' splice site: requirement for U1 small nuclear ribonucleoprotein and the 3' splice site branch point/pyrimidine tract. J Virol. 1999; 73(3):2394-400. PMC: 104485. DOI: 10.1128/JVI.73.3.2394-2400.1999. View

15.

Erlwein O, Buchholz C, Schnierle B . The proline-rich region of the ecotropic Moloney murine leukaemia virus envelope protein tolerates the insertion of the green fluorescent protein and allows the generation of replication-competent virus. J Gen Virol. 2003; 84(Pt 2):369-373. DOI: 10.1099/vir.0.18761-0. View

16.

Domsic J, Wang Y, Mayeda A, Krainer A, Stoltzfus C . Human immunodeficiency virus type 1 hnRNP A/B-dependent exonic splicing silencer ESSV antagonizes binding of U2AF65 to viral polypyrimidine tracts. Mol Cell Biol. 2003; 23(23):8762-72. PMC: 262674. DOI: 10.1128/MCB.23.23.8762-8772.2003. View

17.

Graveley B . Alternative splicing: increasing diversity in the proteomic world. Trends Genet. 2001; 17(2):100-7. DOI: 10.1016/s0168-9525(00)02176-4. View

18.

Zheng Y, Yu H, Peterlin B . Human p32 protein relieves a post-transcriptional block to HIV replication in murine cells. Nat Cell Biol. 2003; 5(7):611-8. DOI: 10.1038/ncb1000. View

19.

Cramer P, Pesce C, Baralle F, Kornblihtt A . Functional association between promoter structure and transcript alternative splicing. Proc Natl Acad Sci U S A. 1997; 94(21):11456-60. PMC: 23504. DOI: 10.1073/pnas.94.21.11456. View

20.

Luo Y, Yu H, Peterlin B . Cellular protein modulates effects of human immunodeficiency virus type 1 Rev. J Virol. 1994; 68(6):3850-6. PMC: 236890. DOI: 10.1128/JVI.68.6.3850-3856.1994. View