According to the Wobble Hypothesis, only the first 2 nucleotides in a codon are critical in the selection of appropriate aa-tRNAs. So, can termination occur because of the UAC and UAU codons (which are codes for tyrosine)?
Before we discuss Francis Crick’s wobble hypothesis, let’s first take a look at how mRNA translation actually ends. Termination of protein synthesis begins when a ribosome arrives at a stop codon within an mRNA sequence, which designates that no additional amino acids should be added to the polypeptide chain. Unlike all its preceding codons, there exist no special tRNA anticodons that will bind through complementary base pairing with any of the UAA, UAG, or UGA stop codons, although that is not entirely true. What I mean to say is that termination of protein synthesis is not mediated by any traditional tRNAs. Instead, we have some competing theories for how translation termination is induced. One mechanism for stop codon recognition is presented by V. Ivanov and partners:In the large ribosomal RNA, we found two sites that, like tRNAs, contain the anticodon hairpin but with triplets complementary to stop codons…By analogy, we call them termination tRNAs: Ter-tRNA1 and Ter-tRNA2, respectively, even though they transport no amino acids, and suggest that they directly pair to stop codons.Their study also claims that additional enzymes named termination factors facilitate precise binding between the ribosomal termination tRNAs and an mRNA’s stop codon. Some researchers call these termination factors “release factors” (RF1, RF2, & RF3), and they see translation termination from a slightly different angle. They claim that, after a long stall in polypeptide synthesis, release factors solely recognize stop codons and induce the release of a finished polypeptide chain while signaling for the ribosomal complex to be disassembled. Although the ideas are fairly similar, I tend to follow the theory proposed by V. Ivanov and partners because it implies a faster production of protein and more specificity for stop codon binding, which would have likely been favored by evolutionBack to the question at hand, could protein synthesis end prematurely due to an incorrect interpretation of stop codon near-cognates such as UAC/UAU? For the sake of our good health, we should dearly hope that is not the case. If there was a chance that protein synthesis would terminate every time the ribosome encountered a Tyrosine/Cysteine/Tryptophan codon which closely resembled a stop codon, we would all arrive to a premature death, making us tonight’s big loser. The wobble hypothesis is simply our best attempt to reason why there exist 61 distinct codons (that code for amino acids) while only about 41 different tRNA anticodons can be detected in our intracellular fluid to match with them. It attempts to explain the complex behavior of tRNA binding to mRNA codons, but it fails to describe recognition of stop codons. This is partly why the wobble hypothesis has remained only a hypothesis for decades. All of our leading theories on the mechanics of translation termination correctly identify that termination tRNAs, or release factors, or what have you, all directly pair with stop codons. They are highly specific in nature, unlike what the wobble hypothesis implies. This is an important distinction. Francis Crick might be correct as far as tRNA/codon interactions are concerned, but the factors involved in translation termination which interact with stop codons are a different story.Any players involved in translation termination know to steer clear of stop codon fakers, but that is not to say that they can’t be fooled. Gene expression in higher-order eukaryotic organisms is highly regulated yet still prone to a few errors every now and then. It would not be surprising to find that a misinterpretation of a near-cognate stop codon might occur, albeit very very rarely, and result in an unfinished polypeptide chain. In these cases, the polypeptide product will most likely lose its intended function because it lacks part of its amino acid sequence. Proteins such as this will be identified and degraded fairly quickly, and ribosomes will make more proteins to replace it.Something else I think you might find interesting is that stop codons sometimes do bind with tRNAs. In a comprehensive study of readthrough evolution in flies and mosquitoes, Irwin Jungreis and partners write:Although a ribosome will normally terminate translation when it encounters one of the three stop codons, UAG, UGA, and UAA, it will sometimes instead insert an amino acid and continue translation in the same frame, adding a peptide extension to that instance of the protein, a phenomenon known as stop codon readthroughThis phenomena is observed in a wide array of viruses (especially RNA), allowing for increased flexibility of their compact genome, and has now been observed in a handful of eukaryotic organisms as well. Modified tRNAs such as selenocysteine tRNA, or other near-cognates of Tyr, Trp, Lys, and Gln, have the capability to undergo noncanonical mismatch at the wobble position and suppress stop codons thereby causing a missense mutation.Sources:A mechanism for stop codon recognition by the ribosome: a bioinformatic approach.Deciphering the reading of the genetic code by near-cognate tRNAEvolutionary Dynamics of Abundant Stop Codon ReadthroughStop codon readthrough generates a C-terminally extended variant of the human vitamin D receptor with reduced response