Epstein–Barr virus U leader exon contains an internal ribosome entry site

Isaksson, Åsa; Berggren, Malin; Ricksten, Anne

doi:10.1038/sj.onc.1206149

Cited by 32 publications

(53 citation statements)

References 39 publications

(37 reference statements)

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“…Neither of these regions contains any known CTL epitopes (16). Mutations in EBNA3B could disrupt the protein's interaction with binding partners, affect the splicing of the internal intron, or compromise the poorly understood alternative splicing process through which the EBNA3s and EBNA1 are joined for their translation (39). However, because no functional domains to our knowledge have been definitively identified in the protein, the functional relevance of specific mutations cannot be predicted.…”

Section: Discussionmentioning

confidence: 91%

EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors

White¹,

Rämer²,

Naresh³

et al. 2012

J. Clin. Invest.

140

159

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Section: Discussionmentioning

confidence: 91%

EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors

White¹,

Rämer²,

Naresh³

et al. 2012

J. Clin. Invest.

140

159

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“…Similarly, the VP2 ORF of the 19S late mRNA of simian virus was found to contain an IRES that controlled the translation of the VP3 ORF. All these IRESs are therefore ICR or within an ORF, with the exception of an IRES that was found within the U leader exon, located within the 5Ј UTR of EBNA1 in Epstein-Barr virus (21). Our finding that an immediate-early gene from MDV-1 contains an IRES at the 5Ј UTR and another IRES at the ICR region, both on the same bicistronic transcript, represents a hybrid situation.…”

mentioning

confidence: 85%

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

Tahiri-Alaoui

Matsuda

et al. 2009

J Virol

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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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“…The transcripts of BGLF4 have long and GC-rich 59UTRs that contain multiple AUG codons. The secondary structure model of the BGLF4 59UTR predicted by the Mfold program (Zuker, 2003) shows a Y-shaped model similar to the 59UTR of EBNA1 (Isaksson et al, 2003). The presence of BGLF3.5 also fits the rule that there is often a short ORF within some IRES structures so that the translation initiation site is involved in ribosome recruitment but does not encode a small protein (Hellen & Sarnow, 2001).…”

Section: Discussionmentioning

confidence: 78%

Characterization of Epstein-Barr virus BGLF4 kinase expression control at the transcriptional and translational levels

Wang

Chuang

Chen

et al. 2010

Journal of General Virology

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The BGLF4 protein of Epstein-Barr virus (EBV) is a serine/threonine protein kinase that phosphorylates several viral and cellular substrates at cellular cyclin-dependent kinase target sites. BGLF4 is required for efficient viral DNA replication and release of mature virions. It also stimulates the transactivation activity of the immediate-early transactivator Zta (BZLF1) and suppresses the transactivation activities of BMRF1 and EBNA-2. This study aimed to characterize further the regulation of BGLF4 expression at the transcriptional and translational levels. It was shown that BGLF4 was expressed with early kinetics and reached maximal levels after DNA replication. The promoter activity of BGLF4 was upregulated mainly by the immediate-early transactivator Rta, rather than Zta, as revealed by Zta-specific short hairpin RNA in EBV-positive cells and by luciferase reporter assays. By rapid amplification of 59 cDNA ends, two major transcriptional start sites were identified at 201 and 255 nt upstream of the first in-frame ATG of BGLF4 in P3HR1 cells. An additional transcript initiated from "468 was detected in Akata cells. The translation initiation site of BGLF4 was confirmed by mutagenesis, in vitro translation and transient transfection. The translation regulatory effect mediated by the long 59-untranslated region (59UTR) of BGLF4 was demonstrated by dual reporter assays in 293T and EBV-positive NA cells. These results suggested that different promoter usage and 59UTR-mediated translation enhancement may ensure the proper expression of BGLF4 at various stages of virus replication.

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Epstein–Barr virus U leader exon contains an internal ribosome entry site

Cited by 32 publications

References 39 publications

EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors

EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors

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

Characterization of Epstein-Barr virus BGLF4 kinase expression control at the transcriptional and translational levels

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