MoBio Initiation Signals of Protein Synthesis Chapter 5

Synthesis of a peptide always starts from methionine. However, the first amino acid of a functional protein is not always methionine. After a peptide is synthesized, it may undergo a variety of modifications, including the cleavage of its N-terminus. Prokaryotes and eukaryotes use different mechanisms to recognize the initiating codon.

Prokaryotes

Many prokaryotic mRNAs are polycistronic, namely, an mRNA encodes more than one peptide chain. The polycistronic mRNA should contain multiple initiating codons. However, a peptide may also contain several non-initiating methionine residues. In the standard genetic code, the codon for both initiating and non-initiating methionine is AUG. To distinguish them, prokaryotes use a specific sequence located about 5-10 bases upstream of the initiation AUG. The specific sequence, UAAGGAGG, is known as the Shine-Dalgamo sequence (after its discoverers).

The 16S rRNA of the ribosome contains a sequence which can pair with the Shine-Dalgamo sequence:

5'--UAAGGAGG(5-10 bases)AUG mRNA

3'--AUUCCUCC........ 16S rRNA

Their association will recruit other parts of the ribosome to the initiation site for protein synthesis.

Eukaryotes

The mechanism used by eukaryotes to recognize the initiating AUG is not entirely clear. Evidence suggests that the eukaryotic ribosome may simply scan from the 5' cap and identify the first AUG as the initiation site. This mechanism is reasonable because nearly all eukaryotic mRNAs are monocistronic (encodes a single peptide). However, some viral mRNAs are polycistronic or lack 5' cap. It is not fully understood how the host eukaryotic cell recognizes the initiation sites of these viral mRNAs. Marilyn Kozak found that the following sequence may increase the effectiveness as an initiation site:

5'--ACCAUGG-        mRNA