The three transfer RNAs occupying the A, P and E sites on the ribosome are involved in viral programmed -1 ribosomal frameshift

Léger, Mélissa; Dulude, Dominic; Steinberg, Sergey V.; Brakier‐Gingras, Léa

doi:10.1093/nar/gkm578

Cited by 61 publications

(86 citation statements)

References 65 publications

(88 reference statements)

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“…Because tRNA near-cognate to the E-site codon could not prevent the incorporation of a noncognate amino acid, the conclusion was that codon-anticodon interaction at the E-site is required to prevent misincorporation at the A-site. This is consistent with the genetic (14,15), biochemical (12,16,17), and structural (18) evidence demonstrating the likelihood of codonanticodon interaction at the E-site.…”

supporting

confidence: 86%

“…The presence of an E-tRNA has been shown to be important for maintaining the reading frame both in vivo (14,15) and in vitro (10) but also, as mentioned above, for preventing the selection of noncognate aminoacyl-tRNAs (5). In the latter experiment, Geigenmüller et al (5) demonstrated that when the E-site was unoccupied, the noncognate acidic Asp (codon GAC/U) could be misincorporated in place of the cognate aromatic hydrophobic Phe (codon UUU/C), however, no misincorporation of Asp was observed when the E-site was occupied.…”

mentioning

confidence: 99%

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Shine–Dalgarno interaction prevents incorporation of noncognate amino acids at the codon following the AUG

Giacco

Márquez

Qin

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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During translation, usually only one in Ϸ400 misincorporations affects the function of a nascent protein, because only chemically similar near-cognate amino acids are misincorporated in place of the cognate one. The deleterious misincorporation of a chemically dissimilar noncognate amino acid during the selection process is precluded by the presence of a tRNA at the ribosomal E-site. However, the selection of first aminoacyl-tRNA, directly after initiation, occurs without an occupied E-site, i.e., when only the P-site is filled with the initiator tRNA and thus should be highly error-prone. Here, we show how bacterial ribosomes have solved this accuracy problem: In the absence of a Shine-Dalgarno (SD) sequence, the first decoding step at the A-site after initiation is extremely error-prone, even resulting in the significant incorporation of noncognate amino acids. In contrast, when a SD sequence is present, the incorporation of noncognate amino acids is not observed. This is precisely the effect that the presence of a cognate tRNA at the E-site has during the elongation phase. These findings suggest that during the initiation phase, the SD interaction functionally compensates for the lack of codon-anticodon interaction at the E-site by reducing the misincorporation of near-cognate amino acids and prevents noncognate misincorporation. E-site ͉ translational errorsT he binding of aminoacyl-tRNAs to the ribosome is dictated by the complementarity between the anticodon of the tRNA and the codon of the mRNA. To ensure the high fidelity of translation, the correct stereochemistry of the mRNA-tRNA codon-anticodon interaction is monitored by components of the small ribosomal subunit in a process known as decoding (reviewed in ref. 1). During decoding, the first and second nucleotide positions (in terms of the codon) of the mRNA-tRNA duplex are closely monitored, whereas interaction at the third or wobble position is less strictly recognized. Consistently, the misincorporation of the wrong amino acids into polypeptide chains usually occurs through the binding of nearcognate aminoacyl-tRNAs, i.e., those tRNAs carrying an anticodon similar to that of the cognate aminoacyl-tRNA, rather than noncognate aminoacyl-tRNAs, which carry dissimilar anticodons. Nascent polypeptide chains are surprisingly tolerant to misincorporation, with only one in Ϸ400 misincorporations being deleterious for the protein's activity (reviewed in ref.2). The reason for this is that usually near-cognate aminoacyl-tRNAs are selected instead of the cognate aminoacyl-tRNA, and the genetic code lexicon is organized in such a way that near-cognate tRNAs bear amino acids that are chemically similar to those carried by the cognate tRNA. For example, the misincorporation of an aspartate (codon: GAU/C) by near-cognate Asp-tRNA, instead of glutamate (GAA/G) by the cognate Glu-tRNA, both incorporate acidic amino acids. The middle and, in most cases, the first position of a codon are almost never misread, even under error-inducing conditions such as high magnesiu...

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supporting

confidence: 86%

mentioning

confidence: 99%

Shine–Dalgarno interaction prevents incorporation of noncognate amino acids at the codon following the AUG

Giacco

Márquez

Qin

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…The function of the E site has been much debated because the E-site tRNA has been observed, in different ensemble studies, to dissociate either before or after binding of the next TC (18)(19)(20). This point is important for the translation mechanism because communication of E-site occupancy to other parts of ribosome has been postulated to increase fidelity of cognate tRNA selection at the ribosomal decoding site (the A site), to preserve reading frame (21,22), to regulate programmed frameshifting (23,24) and to determine the preference of the ribosome for binding either EF-Tu or EF-G (25).…”

mentioning

confidence: 99%

Allosteric vs. spontaneous exit-site (E-site) tRNA dissociation early in protein synthesis

Chen

Stevens

Kaur

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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During protein synthesis, deacylated transfer RNAs leave the ribosome via an exit (E) site after mRNA translocation. How the ribosome regulates tRNA dissociation and whether functional linkages between the aminoacyl (A) and E sites modulate the dynamics of protein synthesis have long been debated. Using single molecule fluorescence resonance energy transfer experiments, we find that, during early cycles of protein elongation, tRNAs are often held in the E site until being allosterically released when the next aminoacyl tRNA binds to the A site. This process is regulated by the length and sequence of the nascent peptide and by the conformational state, detected by tRNA proximity, prior to translocation. In later cycles, E-site tRNA dissociates spontaneously. Our results suggest that the distribution of pretranslocation tRNA states and posttranslocation pathways are correlated within each elongation cycle via communication between distant subdomains in the ribosome, but that this correlation between elongation cycle intermediates does not persist into succeeding cycles.FRET | alternating wavelength laser excitation (ALEX) | multi-translation cycles | classical state | hybrid state

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“…Mutagenesis of the HIV frameshift signal by Horsfield et al (1995) indicated that frameshifting required both the A-and E-site codons in this context. Experiments by a different group using the native HIV stimulatory structure also led to a similar conclusion (Leger et al, 2007). The E-site requirement is also supported by the conservation of certain nucleotides in the E-site position upstream of heptameric slippery sites (Bekaert and Rousset, 2005).…”

Section: Simultaneous Slippagementioning

confidence: 73%

Ribosomal Frameshift Signals in Viral Genomes

Plant¹

2012

Viral Genomes - Molecular Structure, Diversity, Gene Expression Mechanisms and Host-Virus Interactions

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The three transfer RNAs occupying the A, P and E sites on the ribosome are involved in viral programmed -1 ribosomal frameshift

Cited by 61 publications

References 65 publications

Shine–Dalgarno interaction prevents incorporation of noncognate amino acids at the codon following the AUG

Shine–Dalgarno interaction prevents incorporation of noncognate amino acids at the codon following the AUG

Allosteric vs. spontaneous exit-site (E-site) tRNA dissociation early in protein synthesis

Ribosomal Frameshift Signals in Viral Genomes

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