Re: Order of bases in stop codons.

Date: Fri May 1 16:41:55 1998
Posted By: Michael Onken, Grad Student, Wash U
Area of science: Molecular Biology
ID: 892495586.Mb

Message:

The nature of stop codons - in fact, the nature of all codons - is defined by another player in the gene Æ protein pathway: tRNA.

Some background:

RNA comes in several forms, as defined by their functions in the cell: messenger(m)RNA is the transcribed copies of genes which carry their information out of the nucleus to make proteins; ribosomal(r)RNA drives ribosomes to convert the information on mRNA into proteins; transfer(t)RNA brings amino acids to the ribosome to build the proteins; and several RNP's (ribonuclear particles) are involved in editing RNA's and directing protein production. As you mentioned, the Open Reading Frame (ORF) of an mRNA consists of a long string of bases grouped into sets of three called codons, and represents the "blueprint" from which the protein is made. Each ORF is defined by a start codon (AUG, which codes for the amino acid Methionine) and a downstream stop codon (UAA, UAG, or UGA, which don't code for amino acids). Ribosomes use tRNA molecules to read the codons to make proteins.

tRNA:

TranferRNA molecules are small strands of RNA which form cloverleaf shapes through basepairing between portions of the same strand. Each tRNA particle has an anti-codon at one end and an amino acyl acceptor at the other. For each amino acid there are one or more tRNA-amino-acyl- transferase enzymes which bind to tRNA's having a specific base sequence in their anti-codon (like UAC) and attach that specific amino acid (like Methionine). Some amino acids are attached to several different tRNA's (like Serine or Arginine), while others are attached to only one species of tRNA (like Methionine or Tryptophan). So each amino acid is associated with one or more anti-codons as defined by their tRNA's.

Protein Synthesis:

As stated above, Ribosomes use tRNA molecules to read the codons to make proteins. As the mRNA associates with the ribosome, it begins to accumulate tRNA particles which bind to the ORF through basepairing between the codon (e.g. AUG) on the mRNA and the anti-codon (e.g. UAC) on the tRNA. After two or more tRNA's have lined up along the mRNA, the rRNA of the ribosome begins tranfering the amino acids, in order, from the tRNA's to the protein chain. So, the amino acids in a protein are defined by the interactions between tRNA anti-codons and mRNA codons. Obviously, if a codon comes up on the mRNA that doesn't match any of the tRNA anti-codons, then no amino acid can be added in that position. In fact, when a "nonsense" codon appears at the ribosome, the lack of a tRNA bound to it causes the ribosome to completely stop producing protein. That's all a stop codon is: a codon for which there is no tRNA anti-codon. Experiments in bacteria have even shown that you can make new stop codons simply by removing specific tRNA's from a cell. So UAA, UAG, and UGA are stop codons in most eukaryotes because there are no tRNA's with the anti-codons AUU, AUC, or ACU.

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