The structural basis for specific decoding of AUA by isoleucine tRNA on the ribosome

Voorhees, R.M.; Mandal, Debabrata; Neubauer, Cajetan; Köhrer, Caroline; RajBhandary, Uttam L.; Ramakrishnan, V.

doi:10.1038/nsmb.2545

Cited by 39 publications

(53 citation statements)

References 27 publications

(33 reference statements)

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“…5b) shows that they share many structural features (Fig. 5b inset) and, furthermore, that the observed cleavage site is on the same side of the stem structure with respect to the terminal tetraloop 29,30 . However, there are also clear differences between them: although VapC20 cleaves in the tetraloop region of the SRL stem loop, VapCs from enteric bacteria cleave further up the A-form tRNA anticodon stem.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of the crystal structure of the intact Thermus thermophilus 70S (Fig. 5a) shows that helix 95 and the SRL loop are exposed on the surface of the ribosome and therefore would be readily accessible 29 . In addition, the cleavage site within the SRL loop (marked with dark red in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The RNA pellet was briefly washed in ice-cold 70% ethanol before being dried at room temperature and resuspend in nuclease-free water. 30 , shown to the left in gold and that of VapC20, 23S helix 95 or the SRL (T. thermophilus 23S, PDB ID 3ZN9) 29 , right, blue. In both cases, the two nucleotides flanking the cleavage site are highlighted with magenta sticks and labelled.…”

Section: Methodsmentioning

confidence: 99%

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VapC20 of Mycobacterium tuberculosis cleaves the Sarcin–Ricin loop of 23S rRNA

et al. 2013

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The highly persistent and often lethal human pathogen, Mycobacterium tuberculosis contains at least 88 toxin-antitoxin genes. More than half of these encode VapC PIN domain endoribonucleases that inhibit cell growth by unknown mechanisms. Here we show that VapC20 of M. tuberculosis inhibits translation by cleavage of the Sarcin-Ricin loop (SRL) of 23S ribosomal RNA at the same position where Sarcin and other eukaryotic ribotoxins cleave. Toxin-inhibited cells can be rescued by the expression of the antitoxin, thereby raising the possibility that vapC20 contributes to the extreme persistence exhibited by M. tuberculosis. VapC20 cleavage is inhibited by mutations in the SRL that flank the cleavage site but not by changes elsewhere in the loop. Disruption of the SRL stem abolishes cleavage; however, further mutations that restore the SRL stem structure restore cleavage, revealing that the structure rather than the exact sequence of the SRL is important for this activity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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VapC20 of Mycobacterium tuberculosis cleaves the Sarcin–Ricin loop of 23S rRNA

et al. 2013

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“…The agm 2 C-A pair on the ribosome was visualized by solving the crystal structure of the Thermus thermophilus 70S ribosome in complex with archaeal tRNA Ile2 and the AUA codon. 23 At the A-site, agm 2 C34 pairs with A3 of the AUA codon through a single hydrogen bond between N4 of agm 2 C34 and N1 of A3 (Fig. 3C).…”

Section: Aua Decoding By 2-agmatinylcytidinementioning

confidence: 99%

“…23 Crystal with AUA codon will be necessary to solve this issue. Given that tautomerism of the modified base is susceptible to solvent condition with different pH and salt concentration, 26 further structural studies of the base pairing with different solvent conditions are needed for our deeper understanding of AUA decoding by the modified anticodons.…”

Section: Aua Decoding By 2-agmatinylcytidinementioning

confidence: 99%