Cap-independent leaky scanning as the mechanism of translation initiation of a plant viral genomic RNA.

Simón-Buela, Laureano; Guo, Hui; García, Juan-Antonio

doi:10.1099/0022-1317-78-10-2691

Cited by 32 publications

(27 citation statements)

References 28 publications

(32 reference statements)

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“…This translation strategy must differ from the canonical scanning mechanism where the ribosomal complex enters from an accessible 5= end of the mRNA and scans in the 5=-to-3= direction in search and recognition of the 5=-proximal AUG (1). We cannot dismiss, however, whether any of the upstream AUGs play a regulatory role in the recognition and/or regulation of the main initiation site, as observed for the uncapped plum pox virus (PPV) 5= leader (19). Whether the PPV 5= UTR was m7GpppG capped or not, the same level of translation was reported in vitro and in vivo, which supports its ability to drive translation cap independently (19).…”

Section: Discussionmentioning

confidence: 78%

“…Whether the PPV 5= UTR was m7GpppG capped or not, the same level of translation was reported in vitro and in vivo, which supports its ability to drive translation cap independently (19). This 145-nt-long potyviral 5= UTR contains an in-frame upstream AUG at position 36 preceding the authentic initiator AUG at position 147 (19). The PPV leader failed to drive internal initiation in the context of a bicistronic construct.…”

Section: Discussionmentioning

confidence: 84%

“…The PPV leader failed to drive internal initiation in the context of a bicistronic construct. However, when the first AUG codon was placed in a good Kozak sequence context, it became the preferred initiation site (19). This suggests that the correct AUG codon is recognized through a leaky scanning mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…We cannot dismiss, however, whether any of the upstream AUGs play a regulatory role in the recognition and/or regulation of the main initiation site, as observed for the uncapped plum pox virus (PPV) 5= leader (19). Whether the PPV 5= UTR was m7GpppG capped or not, the same level of translation was reported in vitro and in vivo, which supports its ability to drive translation cap independently (19). This 145-nt-long potyviral 5= UTR contains an in-frame upstream AUG at position 36 preceding the authentic initiator AUG at position 147 (19).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the TuMV 5= UTR remains translationally functional in the reverse orientation and such a reverse sequence can inhibit cap-dependent translation in trans (13). In PVY, the 184-nt-long 5= UTR tolerates large deletions within the leader sequence, down to 55 total nucleotides, without major effects on the translation of noncapped monocistronic reporter mRNAs (14,19). The PPV 5= UTR is different yet in that it contains an upstream AUG (uAUG) codon that regulates the translation of the downstream correct AUG start codon via a leaky scanning mechanism (19).…”

mentioning

confidence: 99%

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A Unique 5′ Translation Element Discovered in Triticum Mosaic Virus

Roberts

Zhang

Mayberry

et al. 2015

J Virol

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Several plant viruses encode elements at the 5= end of their RNAs, which, unlike most cellular mRNAs, can initiate translation in the absence of a 5= m7GpppG cap. Here, we describe an exceptionally long (739-nucleotide [nt]) leader sequence in triticum mosaic virus (TriMV), a recently emerged wheat pathogen that belongs to the Potyviridae family of positive-strand RNA viruses. We demonstrate that the TriMV 5= leader drives strong cap-independent translation in both wheat germ extract and oat protoplasts through a novel, noncanonical translation mechanism. Translation preferentially initiates at the 13th start codon within the leader sequence independently of eIF4E but involves eIF4G. We truncated the 5= leader to a 300-nucleotide sequence that drives cap-independent translation from the 5= end. We show that within this sequence, translation activity relies on a stem-loop structure identified at nucleotide positions 469 to 490. The disruption of the stem significantly impairs the function of the 5= untranslated region (UTR) in driving translation and competing against a capped RNA. Additionally, the TriMV 5= UTR can direct translation from an internal position of a bicistronic mRNA, and unlike cap-driven translation, it is unimpaired when the 5= end is blocked by a strong hairpin in a monocistronic reporter. However, the disruption of the identified stem structure eliminates such a translational advantage. Our results reveal a potent and uniquely controlled translation enhancer that may provide new insights into mechanisms of plant virus translational regulation. IMPORTANCEMany members of the Potyviridae family rely on their 5= end for translation. Here, we show that the 739-nucleotide-long triticum mosaic virus 5= leader bears a powerful translation element with features distinct from those described for other plant viruses. Despite the presence of 12 AUG start codons within the TriMV 5= UTR, translation initiates primarily at the 13th AUG codon. The TriMV 5= UTR is capable of driving cap-independent translation in vitro and in vivo, is independent of eIF4E, and can drive internal translation initiation. A hairpin structure at nucleotide positions 469 to 490 is required for the cap-independent translation and internal translation initiation abilities of the element and plays a role in the ability of the TriMV UTR to compete against a capped RNA in vitro. Our results reveal a novel translation enhancer that may provide new insights into the large diversity of plant virus translation mechanisms. T ranslation initiation of most eukaryotic mRNAs occurs by a scanning mechanism, where the 43S ribosomal subunit enters the mRNA from an accessible 5= end, is dependent on the 7-methyl guanosine cap structure (m7GpppG), and scans in a 5=-to-3= direction in search of the initiation codon (1). The ribosomal subunit is recruited to the 5= end by the cap-binding protein factor eIF4E, which is bound to the 5= cap. eIF4E is the small subunit and cap-binding protein in the eIF4F complex. eIF4F is also comprised of the RNA...

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A Unique 5′ Translation Element Discovered in Triticum Mosaic Virus

Roberts

Zhang

Mayberry

et al. 2015

J Virol

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Preservation of 5′-End Integrity of a Potyvirus Genomic RNA Is Not Dependent on Template Specificity

et al. 2000

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Full-length in vitro transcripts of plum pox potyvirus (PPV) genomic RNA with mutations altering the number of 5'-terminal adenosine residues were able to infect Nicotiana clevelandii plants, whereas a mutant with a substitution of adenosine in position 2 by guanosine failed to infect. The genomic 5' end was template-independently repaired during in vivo RNA synthesis producing wild-type viral progeny. Putative models of replication initiation are discussed.

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Design and application of two novel degenerate primer pairs for the detection and complete genomic characterization of potyviruses

et al. 2007

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Two pairs of degenerate primers were designed from sequences within the potyviral CI (CIFor/CIRev) and HC-Pro-coding regions (HPFo/HPRev), and these were shown to be highly specific to members of the genus Potyvirus. Using the CIFor and CIRev primers, three novel potyviruses infecting crop and weed species from Vietnam were detected, namely telosma mosaic virus (TelMV) infecting telosma (Telosma cordata, Asclepiadaceae), peace lily mosaic virus (PeLMV) infecting peace lily (Spathiphyllum patinii, Araceae) and wild tomato mosaic virus (WTMV) infecting wild tomato (Solanum torvum, Solanaceae). The fragments amplified by the two sets of primers enabled additional PCR and complete genomic sequencing of these viruses and a banana bract mosaic virus (BBrMV) isolate from the Philippines. All four viruses shared genomic features typical of potyviruses. Sequence comparisons and phylogenetic analyses indicated that WTMV was most closely related to chilli veinal mottle virus (ChiVMV) and pepper veinal mottle virus (PVMV), while PeLMV, TelMV and BBrMV were related to different extents to members of the bean common mosaic virus (BCMV) subgroup.

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Cap-independent leaky scanning as the mechanism of translation initiation of a plant viral genomic RNA.

Cited by 32 publications

References 28 publications

A Unique 5′ Translation Element Discovered in Triticum Mosaic Virus

A Unique 5′ Translation Element Discovered in Triticum Mosaic Virus

Preservation of 5′-End Integrity of a Potyvirus Genomic RNA Is Not Dependent on Template Specificity

Design and application of two novel degenerate primer pairs for the detection and complete genomic characterization of potyviruses

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