I would be very happy if someone can help me to find the answers for the following related questions.

  1. Can one exon have many stop codons?
  2. Can protein synthesis happen, if the stop codon is at the beginning of the exon?

1 Answer 1


An exon can have multiple stop codons but the first codon will terminate the ORF. The remainder of the exon will be a part of the 3'UTR.

However, there are some cases in which stop codon readthrough happens [1]. In these cases an internal stop codon does not terminate the translation and the ribosome reads through it. During this process an aminoacyl-tRNA successfully competes with the release factor. This is quite evident in the case of selenocysteine and pyrollysine- tRNAs which bind to the UAG (amber) stop codon in certain organisms [2,3] (this is also referred to as amber suppression). The exact mechanisms that affect stop codon readthrough are not elucidated but features in the mRNAs are likely to play a role in this. In case of amber suppression, the relative rarity of the UAG stop codon and lower concentrations of release factor-1, can be major factors.

I don't know what you mean by "beginning of the exon" but there are short ORFs (< 100 codons) which can code for small peptides [4]. Small peptide as small as 6 amino acid residues has been reported but most of the known small peptides are ~30-100 residues long.

[1] Loughran, Gary, et al. "Evidence of efficient stop codon readthrough in four mammalian genes." Nucleic acids research 42.14 (2014): 8928-8938.
[2] Agafonov, Dmitry E., et al. "Efficient suppression of the amber codon in E. coli in vitro translation system." FEBS letters 579.10 (2005): 2156-2160.
[3] Wikipedia: Expanded genetic code
[4] Andrews, Shea J., and Joseph A. Rothnagel. "Emerging evidence for functional peptides encoded by short open reading frames." Nature Reviews Genetics 15.3 (2014): 193-204.

  • $\begingroup$ Thank you for your answer. I have one more clarification. In one of the human protein, i am getting three stop codons (UAG, UAA, UGA). However, i am getting more than 80% of UGA in my transcripts. I appreciate if any one educate me, which is the most frequently present stop codon in human transcripts. $\endgroup$
    – Krithi.S
    Apr 12, 2016 at 11:48
  • $\begingroup$ @Krithi.S I have not checked but this is fairly easy to do. Just download all human mRNA sequences from RefSeq/GTF file with CDS annotations and find the stop codons. $\endgroup$
    Apr 12, 2016 at 12:20
  • $\begingroup$ I'm tempted to link articles from the sixties with me being so old. Amber is the most commonly read through stop codon throughout nature. sciencedirect.com/science/article/pii/S0014579305003224 for a modern example of how it's used $\endgroup$
    – Atl LED
    Apr 12, 2016 at 12:31
  • $\begingroup$ Right that appears to be the mechanism, but it should be noted that it's specific to the Amber stop codon. In bacteria and viruses you can often see doubling or even tripling up of stop codons to prevent Amber readthrough $\endgroup$
    – Atl LED
    Apr 12, 2016 at 12:37
  • 1
    $\begingroup$ @MattDMo the linked article (ref#1) talks about readthrough in human genes $\endgroup$
    Apr 12, 2016 at 17:48

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