Leaky scanning is a mechanism used during the initiation phase of eukaryotic translation that enables regulation of gene expression. During initiation, the small 40S ribosomal subunit (as a 43S PIC) "scans" or moves in a 5' --> 3' direction along the 5'UTR to locate a start codon to commence elongation. Sometimes, the scanning ribosome bypasses the initial AUG start codon and begins translation at further downstream AUG start codons.[1] Translation in eukaryotic cells according to most scanning mechanisms occurs at the AUG start codon proximal to the 5' end of mRNA; however, the scanning ribosome may encounter an “unfavorable nucleotide context” around the start codon and continue scanning.[2]
There are certain instances where initiation has been found to occur upstream at a non-AUG codon. Eukaryotic genes containing consistent G-C rich leader sequences are frequently observed performing this mechanism. It is hypothesized that scanning is slowed due to a secondary structure which allows for the binding of Met-tRNA with the mismatch codon.[3]
Several viruses use a leaky scanning mechanism to produce vital proteins which implies that leaky scanning is not a consequence of inadequacy, but instead allows viruses to overcome the high selective pressures of competing with their hosts.[4] Molecular biologists are narrowing the search of the ideal nucleotide environment for initiation of translation, and the mechanisms by which viruses replicate.[1]