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Is there any reason why AUG is the initiation codon ? Why is there a need for an initiation codon ? Can't translation start with different codons?

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DNA is a sea of nucleotides. How is a transcription enzyme going to know where to start transcribing? –  mgkrebbs Aug 25 '13 at 17:22
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2 Answers 2

up vote 6 down vote accepted

A good question (if a little mixed up on transcription vs. translation!)

AUG is not always the start codon, but whatever the codon is it will always code for Methionine (or fMet, but still a variation on Met), even if the codon codes for a different amino acid otherwise. A separate transfer RNA (tRNAi, the initiator tRNA) is used for the arrangement of this first step, guided by eIF2 [in eukarya].

In this respect it's less a question of "why AUG" than "why this specific initiator tRNA", the answer being that it's got certain sequence elements and modifications that distinguish it from the elongating tRNAs which bind elongation factors and hence are targeted to the ribosomal A and B sites instead of the ribosomal P site (with function being dependent on form, basically it's shaped to set up transcription rather than to elongate an existing nascent chain polypeptide).

"Identity elements appear to finely tune the structure of the initiator tRNA, and growing evidence suggests that the body of the tRNA is involved in transmitting the signal that the start codon has been found to the rest of the pre-initiation complex." — Kolitz and Lorsch, 2010

The other start codons are just from natural chemical variation (or evolution, whichever way you want to look at it) giving rise to different codon-recognising protein shapes.

The machinery for starting translation works, and as such is "conserved" - evolution has kept it, and that's why it is always the same codon (more or less). Archaea have a very similar shaped tRNAi acceptor stem, and is an equally good ligand, which shows how ancient the system is and gives an idea of how fundamentally difficult it must be for an organism to change a system like this through mutation (3.5 billion years of evolution can't be wrong! etc. haha).

Not to just gloss over the part where I said that non-AUG codons get used too (in yeast and mammalian cells), the following is from a study in which it was found changing 1 (and only 1) of the AUG bases still permitted translation initiation:

"Naturally occurring misrecognition indicates that discriminating two base-paired near-cognate codons from the perfect three-base-paired AUG codon is subject to mistakes. Mutations in translation initiation factors, such as eIF1 and eIF2b, further increase the levels of these mistakes.

Two base-pairing interactions between non-AUG codons and the anticodon of the Met-tRNAi are sufficient to trigger translation initiation, suggesting that wild-type eIF1 plays a role in monitoring proper base-pairing interactions when scanning for the AUG start site. It would be predicted that the Met-tRNAi, not a cognate tRNA matching an individual non-AUG codon, is used in translation initiation at these non-AUG start codons.

The translation initiation complex will bind only the Met-tRNAi as opposed to other tRNAs because Met-tRNAi has unique sequence and structural features that allow it to be loaded onto eIF2 of the ternary complex and enable it to fit into the P site of the ribosome" — Maduzia et al, 2010

Basically the consensus is that it's not really possible to say why the methionine codon, "it's just a structural thing", which is a bit of a circular argument really.

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perhaps usage of methionine might have a metabolic reason. Methionine is an essential amino acid and is important for methyltransferases (SAM). So it might be vaguely possible that using Met for initiation is a metabolic checkpoint. –  WYSIWYG Sep 4 '13 at 8:26
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First of all, it is the transcript and not the gene that starts with an AUG. Also, there are actually quite a few transcripts that start with different initiation codons, they are just the exceptions rather than the norm.

As for the need, you can think of START and STOP codons as punctuation. The AUG is read like the first (capital) letter of a sentence (if you will allow me to stretch the definition of punctuation a little). Read up on the process of translation, the ribosome will attach to the mRNA molecule which includes UTRs, it uses the AUG codon as an indication that it should now start translating.

UTRs are the untranslated regions and often contain regulatory sequences that can control translation. However, these should not be in the final protein product so the cellular machinery needs a way of knowing where the UTR ends and the coding sequence begins.

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I could not understand the first line.Please help. –  biogirl Aug 26 '13 at 12:23
    
@biogirl I think lmmx explained it perfectly but a gene consists of much more than the protein coding transcript. Genes typically include promoters, enhancers, various splicing signals, introns etc. AUG (usually) marks the start of translation, the sequence that codes for proteins it does not mark the start of the gene. –  terdon Aug 26 '13 at 15:00
    
Thanks ! I really had a wrong concept. –  biogirl Aug 26 '13 at 15:59
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