The 5' Leader of the MRNA Encoding the Marek's Disease Virus Serotype 1 Pp14 Protein Contains an Intronic Internal Ribosome Entry Site with Allosteric Properties

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2009 Oct 2

PMID 19793814

Citations 7

Authors

Abdessamad Tahiri-Alaoui

Daiki Matsuda

Hongtao Xu

Panopoulos Panagiotis

Luke Burman

Luke S Lambeth

Lawrence Petherbridge

William James

Vincent Mauro

Venugopal Nair

Affiliations

Soon will be listed here.

Abstract

We demonstrate the presence of a functional internal ribosome entry site (IRES) within the 5' leader (designated 5L) from a variant of bicistronic mRNAs that encode the pp14 and RLORF9 proteins from Marek's disease virus (MDV) serotype 1. Transcribed as a 1.8-kb family of immediate-early genes, the mature bicistronic mRNAs have variable 5' leader sequences due to alternative splicing or promoter usage. Consequently, the presence or absence of the 5L IRES in the mRNA dictates the mode of pp14 translation and leads to the production of two pp14 isoforms that differ in their N-terminal sequences. Real-time reverse transcription-quantitative PCR indicates that the mRNA variants with the 5L IRES is two to three times more abundant in MDV-infected and transformed cells than the mRNA variants lacking the 5L IRES. A common feature to all members of the 1.8-kb family of transcripts is the presence of an intercistronic IRES that we have previously shown to control the translation of the second open reading frame (i.e., RLORF9). Investigation of the two IRESs residing in the same bicistronic reporter mRNA revealed functional synergism for translation efficiency. In analogy with allosteric models in proteins, we propose IRES allostery to describe such a novel phenomenon. The functional implications of our findings are discussed in relation to host-virus interactions and translational control.

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References

Bulow V, Biggs P . Differentiation between strains of Marek's disease virus and turkey herpesvirus by immunofluorescence assays. Avian Pathol. 1975; 4(2):133-46. DOI: 10.1080/03079457509353859. View

Haghighat A, Mader S, Pause A, Sonenberg N . Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J. 1995; 14(22):5701-9. PMC: 394685. DOI: 10.1002/j.1460-2075.1995.tb00257.x. View

Tahiri-Alaoui A, Smith L, Baigent S, Kgosana L, Petherbridge L, Lambeth L . Identification of an intercistronic internal ribosome entry site in a Marek's disease virus immediate-early gene. J Virol. 2009; 83(11):5846-53. PMC: 2681985. DOI: 10.1128/JVI.02602-08. View

Kuriyan J, Eisenberg D . The origin of protein interactions and allostery in colocalization. Nature. 2007; 450(7172):983-90. DOI: 10.1038/nature06524. View

Isaksson A, Berggren M, Ricksten A . Epstein-Barr virus U leader exon contains an internal ribosome entry site. Oncogene. 2003; 22(4):572-81. DOI: 10.1038/sj.onc.1206149. View

Sarnow P . Viral internal ribosome entry site elements: novel ribosome-RNA complexes and roles in viral pathogenesis. J Virol. 2003; 77(5):2801-6. PMC: 149783. DOI: 10.1128/jvi.77.5.2801-2806.2003. View

Buckmaster A, Scott S, Sanderson M, Boursnell M, Ross N, Binns M . Gene sequence and mapping data from Marek's disease virus and herpesvirus of turkeys: implications for herpesvirus classification. J Gen Virol. 1988; 69 ( Pt 8):2033-42. DOI: 10.1099/0022-1317-69-8-2033. View

Bradley G, Lancz G, Tanaka A, Nonoyama M . Loss of Marek's disease virus tumorigenicity is associated with truncation of RNAs transcribed within BamHI-H. J Virol. 1989; 63(10):4129-35. PMC: 251026. DOI: 10.1128/JVI.63.10.4129-4135.1989. View

Hughes T . Regulation of gene expression by alternative untranslated regions. Trends Genet. 2006; 22(3):119-22. DOI: 10.1016/j.tig.2006.01.001. View

10.

Jin L, Guzik B, Bor Y, Rekosh D, Hammarskjold M . Tap and NXT promote translation of unspliced mRNA. Genes Dev. 2004; 17(24):3075-86. PMC: 305259. DOI: 10.1101/gad.1155703. View

11.

Reddy S, Lupiani B, Gimeno I, Silva R, Lee L, Witter R . Rescue of a pathogenic Marek's disease virus with overlapping cosmid DNAs: use of a pp38 mutant to validate the technology for the study of gene function. Proc Natl Acad Sci U S A. 2002; 99(10):7054-9. PMC: 124527. DOI: 10.1073/pnas.092152699. View

12.

Xu H, Yao Y, Zhao Y, Smith L, Baigent S, Nair V . Analysis of the expression profiles of Marek's disease virus-encoded microRNAs by real-time quantitative PCR. J Virol Methods. 2008; 149(2):201-8. DOI: 10.1016/j.jviromet.2008.02.005. View

13.

Hernandez G . Was the initiation of translation in early eukaryotes IRES-driven?. Trends Biochem Sci. 2008; 33(2):58-64. DOI: 10.1016/j.tibs.2007.11.002. View

14.

Kawamura M, Hayashi M, Furuichi T, Nonoyama M, Isogai E, NAMIOKA S . The inhibitory effects of oligonucleotides, complementary to Marek's disease virus mRNA transcribed from the BamHI-H region, on the proliferation of transformed lymphoblastoid cells, MDCC-MSB1. J Gen Virol. 1991; 72 ( Pt 5):1105-11. DOI: 10.1099/0022-1317-72-5-1105. View

15.

Petherbridge L, Brown A, Baigent S, Howes K, Sacco M, Osterrieder N . Oncogenicity of virulent Marek's disease virus cloned as bacterial artificial chromosomes. J Virol. 2004; 78(23):13376-80. PMC: 525015. DOI: 10.1128/JVI.78.23.13376-13380.2004. View

16.

Hong Y, Frame M, Coussens P . A 14-kDa immediate-early phosphoprotein is specifically expressed in cells infected with oncogenic Marek's disease virus strains and their attenuated derivatives. Virology. 1995; 206(1):695-700. DOI: 10.1016/s0042-6822(95)80091-3. View

17.

Bieleski L, Talbot S . Kaposi's sarcoma-associated herpesvirus vCyclin open reading frame contains an internal ribosome entry site. J Virol. 2001; 75(4):1864-9. PMC: 114096. DOI: 10.1128/JVI.75.4.1864-1869.2001. View

18.

Chappell S, Edelman G, Mauro V . A 9-nt segment of a cellular mRNA can function as an internal ribosome entry site (IRES) and when present in linked multiple copies greatly enhances IRES activity. Proc Natl Acad Sci U S A. 2000; 97(4):1536-41. PMC: 26470. DOI: 10.1073/pnas.97.4.1536. View

19.

Han F, Zhang X . Internal initiation of mRNA translation in insect cell mediated by an internal ribosome entry site (IRES) from shrimp white spot syndrome virus (WSSV). Biochem Biophys Res Commun. 2006; 344(3):893-9. DOI: 10.1016/j.bbrc.2006.03.229. View

20.

Mauro V, Chappell S, Dresios J . Analysis of ribosomal shunting during translation initiation in eukaryotic mRNAs. Methods Enzymol. 2007; 429:323-54. DOI: 10.1016/S0076-6879(07)29015-9. View