Human adenovirus encodes two proteins which have opposite effects on accumulation of alternatively spliced mRNAs.

Nordqvist, Katarina; Ohman, K; Akusjärvi, Göran

doi:10.1128/mcb.14.1.437

Cited by 68 publications

(54 citation statements)

References 40 publications

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“…At late times of infection E1B-55K and E4orf6 are localized within and at the periphery of nuclear viral inclusions, believed to be the sites of viral transcription and/or replication (Ornelles and Shenk, 1991). This observation is consistent with the idea that this viral protein complex regulates RNA transport at an intranuclear step possibly by facilitating the movement of mature viral mRNAs to the nuclear pore complex (Dix and Leppard, 1993;Leppard, 1993;Nordqvist et al, 1994). The E1B-55K protein not only plays a critical role during viral replication but appears to be also involved in the processes of transformation (Moore et al, 1996).…”

Section: Introductionsupporting

confidence: 89%

The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2

et al. 2000

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The E1B-55K and E4orf6 oncoproteins of adenovirus type 5 are involved in the export of viral mRNAs. Previously, it was suggested that a complex composed of E1B-55K and E4orf6 serves as a nucleocytoplasmic transporter for viral mRNAs in which the E4orf6 protein directs both nuclear import and export. We now demonstrate that the E1B-55K protein itself shuttles e ciently in the absence of E4orf6. In addition, E1B-55K tra cking was independent of the de®ned shuttle proteins Mdm2 or p53, which interacts with E1B-55K. The identi®ed N-terminal E1B-55K leucine-rich nuclearexport signal (NES) conferred rapid nuclear export even in a heterologous system in contrast to the postulated E4orf6NES. Interestingly, although shuttling was blocked by inhibitors of the CRM1 mediated export pathway, E1B-55K inhibited neither the activity nor the tra cking of the retroviral shuttle proteins HIV-1 Rev and HTLV-1 Rex. In contrast, Rev or Rex blocked the nuclear export of E1B-55K, most likely by competing for essential export factors. Our results provide new insights into the regulation of the adenovirus mRNA export system and the processes of adenovirus mediated transformation. Oncogene (2000) 19, 850 ± 857.

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Section: Introductionsupporting

confidence: 89%

The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2

et al. 2000

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“…However, if either E1B-55K or E4orf6 is absent, E4orf3 is required for viral replication, and the E4orf3 function is more effective in Sphase-infected cells than in G 1 -infected cells. Potential functions for E4orf3 in this context may include the regulation of mRNA processing (11), the promotion of mRNA transport (2), the inhibition of host translation, the suppression of host antiviral responses, or the prevention of viral DNA concatemer formation (14). The findings reported here may also be significant for the development of oncolytic Ads for the treatment of cancer.…”

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confidence: 77%

E4orf3 Is Necessary for Enhanced S-Phase Replication of Cell Cycle-Restricted Subgroup C Adenoviruses

Shepard

Ornelles

2003

J Virol

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“…In addition, all of these experiments were conducted without proteins from the E4 gene; the relative levels of expression of E4 Orf3 and Orf6 have been shown to affect i-leader inclusion (35,36). The level of L3 hexon mRNA in cytoplasmic RNA from pBiL1-3-transfected cells was at least 50-fold less than in RNA from pBiL1-5-transfected cells (Fig.…”

Section: Vol 78 2004mentioning

confidence: 99%

“…An optional fourth exon, called the i-leader, is inserted between leaders 2 and 3 in the majority of L1 52/55K mRNA produced at early times, whereas it is mostly excluded from this and all other MLTU mRNAs at late times (8). The inclusion or exclusion of the i-leader is regulated by E4 Orf3 and E4 Orf6, respectively (35,36), and its presence destabilizes the mRNA (42).…”

mentioning

confidence: 99%

Activation of the Early-Late Switch in Adenovirus Type 5 Major Late Transcription Unit Expression by L4 Gene Products

Farley

Brown

Leppard

2004

J Virol

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The adenovirus major late transcription unit (MLTU) encodes multiple proteins from five regions, L1 to L5, through differential splicing and polyadenylation. MLTU expression is temporally regulated; only a single product from L1 (52/55K) is expressed prior to replication, but a subsequent switch, the mechanism of which has not been defined, leads to full expression that encompasses L1 IIIa and all L2 to L5 products. Transfection of a plasmid containing the complete MLTU gave a full array of proteins in proportions similar to those in a late infection, and in a time course, the temporal pattern of expression in a natural infection was reproduced. However, a plasmid truncated after the L3 poly(A) site exclusively expressed the L1 52/55K protein and was defective in the switch to full gene expression from L1 to L3. The L4 33K protein, supplied in trans, was sufficient to upregulate cytoplasmic mRNA for MLTU products characteristic of the late pattern of expression to levels comparable to those produced by the full-length MLTU. There was a corresponding increase in expression of the L1 IIIa, L2, and L3 proteins, except hexon. Hexon protein expression additionally required both the L4 100K protein in trans and sequences downstream of the L3 poly(A) site in cis. These results indicate that induction of L4 protein expression is a key event in the early-late switch in MLTU expression, which we propose is precipitated by small amounts of L4 expression in a feed-forward activation mechanism.Human adenoviruses, especially group C viruses such as serotype 5 (Ad5), have been studied extensively; their tropism, gene expression, host cell interactions, and transforming capabilities are well characterized. Despite this knowledge, however, there remain important aspects of adenovirus biology that are not understood. One of these is the control of protein expression from the major late transcription unit (MLTU) during the infectious cycle.Upon Ad5 infection, a temporally phased program of gene expression occurs. The E1A gene products are produced immediately and upregulate transcription from all of the early regions: E1A, E1B, E2, E3, and E4. The MLTU, which encodes the majority of the virus structural proteins within five subregions, L1 to L5, is also active at a low level during this early phase, but transcription proceeds only as far as the L3 region and mRNA production is focused on the L1 52/55K reading frame (33). After replication, the major late promoter (MLP) becomes fully activated and transcription is allowed to proceed through the full length of the MLTU to supply the proteins for the packaging of newly replicated genomes into virions. The MLP is activated by the E1A 289R protein (32) and also by the intermediate-late protein IVa2 (28). However, unreplicated genomes from virus allowed to superinfect cells already in the late phase of infection, and hence containing these activators, continue to display the early pattern of MLTU expression until they themselves have begun to replicate (44). This indicates a role for a ...

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Human adenovirus encodes two proteins which have opposite effects on accumulation of alternatively spliced mRNAs.

Abstract: All mRNAs expressed from the adenovirus major late transcription unit have a common, 201-nucleotide-long 5' leader sequence, which consists of three short exons (the tripartite leader). This leader has two

Cited by 68 publications

References 40 publications

The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2

The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2

E4orf3 Is Necessary for Enhanced S-Phase Replication of Cell Cycle-Restricted Subgroup C Adenoviruses

Activation of the Early-Late Switch in Adenovirus Type 5 Major Late Transcription Unit Expression by L4 Gene Products

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