A potential mechanism for selective control of cap-independent translation by a viral RNA sequence in cis and in trans

Wang, Shanping; Guo, Liang; Allen, Edwards; Miller, W. Allen

doi:10.1017/s1355838299981979

Cited by 52 publications

(99 citation statements)

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“…In vitro, sgRNA2, which contains the 3ЈTE in its 5Ј untranslated region (UTR), strongly inhibits translation of the gRNA in trans but only weakly inhibits translation of sgRNA1 (49). Thus, we suggest that sgRNA2, which can accumulate to a 20-to 40-fold molar excess over gRNA, mediates a switch from early (replicase) to late (coat protein) gene expression (47). Understanding sgRNA2 transcriptional regulation will help us test this model.…”

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confidence: 94%

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A Positive-Strand RNA Virus with Three Very Different Subgenomic RNA Promoters

Koev

Miller

2000

J Virol

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Numerous RNA viruses generate subgenomic mRNAs (sgRNAs) for expression of their 3-proximal genes. A major step in control of viral gene expression is the regulation of sgRNA synthesis by specific promoter elements. We used barley yellow dwarf virus (BYDV) as a model system to study transcriptional control in a virus with multiple sgRNAs. BYDV generates three sgRNAs during infection. The sgRNA1 promoter has been mapped previously to a 98-nucleotide (nt) region which forms two stem-loop structures. It was determined that sgRNA1 is not required for BYDV RNA replication in oat protoplasts. In this study, we show that neither sgRNA2 nor sgRNA3 is required for BYDV RNA replication. The promoters for sgRNA2 and sgRNA3 synthesis were mapped by using deletion mutagenesis. The minimal sgRNA2 promoter is approximately 143 nt long (nt 4810 to 4952) and is located immediately downstream of the putative sgRNA2 start site (nt 4809). The minimal sgRNA3 core promoter is 44 nt long (nt 5345 to 5388), with most of the sequence located downstream of sgRNA3 start site (nt 5348). For both promoters, additional sequences upstream of the start site enhanced sgRNA promoter activity. These promoters contrast to the sgRNA1 promoter, in which almost all of the promoter is located upstream of the transcription initiation site. Comparison of RNA sequences and computerpredicted secondary structures revealed little or no homology between the three sgRNA promoter elements. Thus, a small RNA virus with multiple sgRNAs can have very different subgenomic promoters, which implies a complex system for promoter recognition and regulation of subgenomic RNA synthesis.

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confidence: 94%

“…We proposed recently that sgRNA2 plays a role in translational regulation of BYDV gene expression (47). Unlike the majority of eukaryotic mRNAs, BYDV genomic RNA is uncapped (2).…”

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A Positive-Strand RNA Virus with Three Very Different Subgenomic RNA Promoters

Koev

Miller

2000

J Virol

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“…The BTE sequence that is necessary and sufficient for capindependent translation of BYDV RNA in wheat germ extract (wge) resides within a 105-nt tract (BTE105) between bases 4814 and 4918 at the 59 end of the 39UTR ( Fig. 1A; Wang and Miller 1995;Wang et al 1997Wang et al , 1999Guo et al 2000). The BTE105 sequence alone represses translation of viral and nonviral mRNAs when added in trans Shen et al 2006).…”

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confidence: 99%

The 3′ cap-independent translation element of Barley yellow dwarf virus binds eIF4F via the eIF4G subunit to initiate translation

Treder

Kneller

Allen

et al. 2007

RNA

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146

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The 39 cap-independent translation element (BTE) of Barley yellow dwarf virus RNA confers efficient translation initiation at the 59 end via long-distance base pairing with the 59-untranslated region (UTR). Here we provide evidence that the BTE functions by recruiting translation initiation factor eIF4F. We show that the BTE interacts specifically with the cap-binding initiation factor complexes eIF4F and eIFiso4F in a wheat germ extract (wge). In wge depleted of cap-interacting factors, addition of eIF4F (and to a lesser extent, eIFiso4F) allowed efficient translation of an uncapped reporter construct (BLucB) containing the BTE in its 39 UTR. Translation of BLucB required much lower levels of eIF4F or eIFiso4F than did a capped, nonviral mRNA. Both full-length eIF4G and the carboxy-terminal half of eIF4G lacking the eIF4E binding site stimulated translation to 70% of the level obtained with eIF4F, indicating a minor role for the cap-binding protein, eIF4E. In wge inhibited by either BTE in trans or cap analog, eIF4G alone restored translation nearly as much as eIF4F, while addition of eIF4E alone had no effect. The BTE bound eIF4G (Kd = 177 nm) and eIF4F (Kd = 37 nm) with high affinity, but very weakly to eIF4E. These interactions correlate with the ability of the factors to facilitate BTE-mediated translation. These results and previous observations are consistent with a model in which eIF4F is delivered to the 59 UTR by the BTE, and they show that eIF4G, but not eIF4E, plays a major role in this novel mechanism of cap-independent translation.

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“…Barley yellow dwarf virus (BYDV) RNA, a luteovirus, also lacks a 5Ј cap structure (37). Wang and Miller (38) previously identified a cap-independent translational enhancer (TE) domain located within the 3Ј-UTR of BYDV.…”

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“…Wang and Miller (38) previously identified a cap-independent translational enhancer (TE) domain located within the 3Ј-UTR of BYDV. The TE stimulates translation of viral and heterologous genes 30 -100-fold (38), and inactivation of this enhancer region renders BYDV RNA cap-dependent (37,39). The addition of the BYDV TE domain in trans specifically inhibits in vitro translation and is reversed by the addition of eIF4F (39).…”

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A Novel Interaction of Cap-binding Protein Complexes Eukaryotic Initiation Factor (eIF) 4F and eIF(iso)4F with a Region in the 3′-Untranslated Region of Satellite Tobacco Necrosis Virus

Gazo

Murphy

Gatchel

et al. 2004

Journal of Biological Chemistry

108

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Satellite tobacco necrosis virus (STNV)RNA is naturally uncapped at its 5 end and lacks polyadenylation at its 3 end. Despite lacking these two hallmarks of eukaryotic mRNAs, STNV-1 RNA is translated very efficiently. A ϳ130-nucleotide translational enhancer (TED), located 3 to the termination codon, is necessary for efficient cap-independent translation of STNV-1 RNA. The STNV-1 TED RNA fragment binds to the eukaryotic cap-binding complexes, initiation factor (eIF) 4F and eIF(iso)4F, as measured by nitrocellulose binding and fluorescence titration. STNV-1 TED is a potent inhibitor of in vitro translation when added in trans. This inhibition is reversed by the addition of eIF4F or eIF(iso)4F, and the subunits of eIF4F and eIF(iso)4F cross-link to STNV-1 TED, providing additional evidence that these factors interact directly with STNV-1 TED. Deletion mutagenesis of the STNV-1 TED indicates that a minimal region of ϳ100 nucleotides is necessary to promote cap-independent translation primarily through interaction with the cap binding subunits (eIF4E or eIF(iso)4E) of eIF4F or eIF(iso)4F.Initiation of protein synthesis in eukaryotic cells is a complicated process requiring 8 -10 initiation factors for proper alignment of the initiation codon of messenger RNA on the 40 S ribosome and subsequent joining of the 60 S ribosome (for review, see Refs. 1-6). For eukaryotes the first step in this process is the recognition of the m 7 GpppX cap structure at the 5Ј end of mRNA by eIF4E, 1 the cap-binding protein component of the eIF4F complex. The eIF4G component of eIF4F then acts as a scaffold for the assembly of other initiation factors (for review, see Refs. 7-11). Initiation factors eIF4A, eIF3, and poly(A)-binding protein (PABP) are known to interact with eIF4G during this process (for review, see Refs. 7, 9, and 10). PABP binds the poly(A) tail present at the 3Ј end of most cellular mRNAs, and the interaction of PABP with eIF4G implies that the 5Ј and 3Ј ends of the cellular mRNA are brought into close proximity during the initiation process (for review, see Refs. 9 and 12). This assembly of factors on the mRNA presumably functions in an ATP-dependent unwinding of secondary structure in the 5Ј-UTR of the mRNA before binding and scanning of the 40 S ribosome to find the correct initiation codon (5).Plant eIF4F consists of two subunits, a small cap-binding protein, eIF4E (26 kDa), and a large subunit, eIF4G (180 kDa). Higher plants possess an isozyme form of eIF4F, termed eIF(iso) 4F (13, 14). eIF(iso)4F, like eIF4F, consists of two subunits, eIF(iso)4E (28 kDa), and a large subunit, eIF(iso)4G (86 kDa). eIF(iso)4F has functions similar to eIF4F in the initiation of translation of plant mRNAs (14). The amino acid sequence of plant eIF(iso)4E is ϳ50% similar to plant eIF4E and retains all the conserved tryptophan residues found in cap-binding proteins (15,16). The large subunit, eIF(iso)4G, is significantly smaller than plant eIF4G (86 versus 180 kDa, (15)), sharing ϳ30 -40% similarity with central and C-terminal regions o...

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A potential mechanism for selective control of cap-independent translation by a viral RNA sequence in cis and in trans

Cited by 52 publications

References 46 publications

A Positive-Strand RNA Virus with Three Very Different Subgenomic RNA Promoters

A Positive-Strand RNA Virus with Three Very Different Subgenomic RNA Promoters

The 3′ cap-independent translation element of Barley yellow dwarf virus binds eIF4F via the eIF4G subunit to initiate translation

A Novel Interaction of Cap-binding Protein Complexes Eukaryotic Initiation Factor (eIF) 4F and eIF(iso)4F with a Region in the 3′-Untranslated Region of Satellite Tobacco Necrosis Virus

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