Leaky scanning is a mechanism utilized in translation of eukaryotic cells that allows for 40s ribosomal subunits to bypass the initial AUG start codon and begin translation at further downstream AUG start codons. Translation in eukaryotic cells according to most scanning mechanisms occurs at the AUG start codon proximal to the 5’end of mRNA. When specific 40s ribosomal subunits scan mRNA beginning at the 5’end it may encounter an “unfavorable context” around the start codon. Commonly, leaky scanning occurs due to a multitude of defects surrounding this start codon’s “nucleotide context”.
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.
Several viruses utilize a leaky scanning mechanism to produce numerous vital proteins which implies that leaky scanning is not a consequence of inadequacy. The utilization of this allows viruses to overcome the high selective pressures of competing with their hosts and provide a specific function for replication. Molecular biologists are narrowing the search of the ideal nucleotide environment for initiation of translation, and the mechanisms by which viruses replicate.
Through several studies Marilyn Kozak was the first to recognize the main role of scanning during initiation of translation in mammalian cells. The AUG codon in mammals is optimally recognized by the context GCCRCCAUGG, also known as a “Kozak Consensus Sequence.” Purine (R) and each of the nucleotides within this sequence are highly conserved and provide an important function in recognition and initiation of translation for many 40s ribosomal subunits. With an optimal context at an AUG start codon ribosomes will begin initiation at that point. A weak context occurs when the sequences adjacent to the AUG start codon has deviated from the consensus sequence. A few ribosomes will still initiate translation in the weak location but the majority will perform leaky scanning and initiation downstream. As a consequence different proteins are likely to be produced (e.g. viral proteins).
Every day, more examples of leaky scanning are becoming apparent in plant and animal viruses. Learning about the variety of exceptions of scanning during translation initiation provides scientists with the means to understand the role of leaky scanning in viral replication. There are several unidentified mechanisms involved with this overall process; particularly the with unknown secondary structures that affect scanning and binding of nucleotides.
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