Assume a mutation in the CCA arm of tRNAThr occurs that reduces the flexibility of this region of the molecule but still allows the 3′ end of the tRNA to enter the aminoacyl-tRNA synthetase activation site. Which of the following is the most likely outcome?

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BlackTom AI · Accepted Answer

Consider the scenario: a mutation in the CCA arm of tRNAThr reduces flexibility but still permits the 3′ end to enter the aminoacyl-tRNA synthetase activation site. This setup specifically tests whether misacylation can occur and whether the proofreading/editing function can correct it.
Option 1: 'The tRNAThr may become charged with Ser but will not undergo proofreading.' This option suggests that Ser could be attached and that no proofreading/editing would occur. In many aminoacyl-tRNA synthetases, including threonyl-tRNA synthetase (ThrRS), there is an editing mechanism that hydrolyzes misactivated Ser on tRNAThr after charging. Therefore, it is unlikely that proofreading would be completely absent if mischarging happened; the system typically has a corrective step. So this statement ignores the known proofreading feature of ThrRS.
Option 2: 'The tRNAThr will never be attached to Ser.' While the mutation could potentially reduce specificity, the question describes a condition where the 3′ end can still reach the activation site, opening the possibility that Ser could be activated and transferred. Saying it will *never* be charged with Ser is overly absolute and disregards possible misactivation and transient mischarging that proofreading would then address.
Option 3: 'The tRNAThr will never be attached to Thr.' This is inconsistent with the described scenario where the activation site can be reached; if the tRNA can access the site, the cognate amino acid Thr could still be attached. The premise does not support a guaranteed block to Thr charging.
Option 4: 'The tRNAThr may become charged with Ser but will undergo proofreading to remove the Ser.' This aligns with known biology: ThrRS can misactivate Ser and attach it to tRNAThr, but ThrRS possesses an editing function that removes mischarged Ser from tRNAThr, restoring correct charging or preventing misincorporation. The reduced flexibility could increase the chance of misactivation, but the editing mechanism would act to correct it, making this the most plausible outcome among the options.
Overall, options 1 and 2 oversimplify or dismiss the editing capability, option 3 ignores the described access to the activation site, while option 4 captures the plausible mischarging event followed by editing-based correction, which fits established mechanisms of kinetic proofreading and post-transfer editing in aminoacyl-tRNA synthetases.

BIOL3611.13541.202610 LA4SP2025

Assume a mutation in the CCA arm of tRNAThr occurs that reduces the flexibility of this region of the molecule but still allows the 3′ end of the tRNA to enter the aminoacyl-tRNA synthetase activation site. Which of the following is the most likely outcome?

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