MICROBIOLOGY AND IMMUNOLOGY ON-LINE

Eucaryotic messenger mRNAs have a methyl cap at the 5' end which is necessary for efficient translation to occur. Also necessary, of course, is the initiation AUG codon and frequently this is the first AUG that the ribosome encounters after binding at the 5' end of the message.  If the distance between the 5' cap and the initation AUG is about 40 nucleotides or less , the ribosome can bind to both. However, the distance between these two points may be much longer, up to 1000 or more nucleotides. It appears that the ribosome moves along the 5' region of the molecule to find both sites. Initially, the 40S subunit binds to the methyl cap and migrates along the mRNA, a process called scanning. This scanning also gets rid of some of the secondary base-pairing structure that may occur in this region of the message. The movement of the 40S subunit ceases when it finds the AUG codon that will code for the initiator methionine of the protein. In most cases, this is the first AUG that it encounters but this is not always true. How does the ribosome know at which AUG to start?  The AUG has to be in the correct context which is 5' PCCAUGG 3'. In this sequence the underlined codon is the initiation codon and P stands for a purine (A or G). This purine and the G after the initiation codon are the most important indicators of the true start of the protein.  This sequence is the Kosak sequence discovered by Marilyn Kosak.

In bacteria, a sequence called the Shine-Dalgano sequence is important in defining the initiator AUG.  This is a polypurine stretch near the 5' end of the message (AGGAGG) and initiation of protein synthesis occurs  at the next AUG downstream (towards the 3' end)