Leaky scanning is a mechanism used during the initiation phase of

eukaryotic translation Eukaryotic translation is the biological process by which messenger RNA is Translation (biology), translated into proteins in eukaryotes. It consists of four phases: initiation, elongation, termination, and recapping. Initiation Translation init ...

that enables regulation of

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

. During initiation, the small 40S ribosomal subunit (as a 43S PIC) "scans" or moves in a 5' --> 3' direction along the

5'UTR The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly upstream from the initiation codon. This region is important for the regulation of ...

to locate a

start codon The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and archaea and a ''N''-formylmethionine (fMet) in bacteria, mitochondria and plastids. ...

to commence elongation. Sometimes, the scanning ribosome bypasses the initial AUG start codon and begins translation at further downstream AUG start codons.Kozak, Marilyn. “Initiation of Translation in prokaryotes and eukaryotes.” Gene 234 (1999): 187-208. Academic Search Complete. Web. 10 June 2014. Translation in eukaryotic cells according to most scanning mechanisms occurs at the AUG start codon proximal to the 5' end of

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

; however, the scanning ribosome may encounter an “unfavorable nucleotide context” around the start codon and continue scanning.Herzog, Etienne., et al. “Translation of the Second Gene of Peanut Clump Virus RNA 2 Occurs by Leaky Scanning In Vitro.” Virology 208. (1995): 215-225. Academic Search Complete. Web. 10 June 1014. 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 Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

with the mismatch codon.Kozak, Marilyn. “Pushing the limits of the scanning mechanism of initiation of translation.” Gene 299 (2002): 1-34. Academic Search Complete. Web. 11 June 2014. Several

virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...

es use a leaky scanning mechanism to produce viral

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s which implies that leaky scanning is not a consequence of inadequacy, but instead allows viruses to overcome the high

selective pressure Evolutionary pressure, selective pressure or selection pressure is exerted by factors that reduce or increase reproductive success in a portion of a population, driving natural selection. It is a quantitative description of the amount of change oc ...

s of competing with their hosts.Ryaboba, Lyubov., et al. “Translation reinitiation and leaky scanning in plant viruses.” Virus Research 119 (2006): 52-62 Academic Search Complete. Web. 23 June 2014. Molecular biologists are narrowing the search of the ideal nucleotide environment for initiation of translation, and the mechanisms by which viruses replicate.

Discovery

Through several studies

Marilyn Kozak Marilyn S. Kozak is an American professor of biochemistry at the Robert Wood Johnson Medical School. She was previously at the University of Medicine and Dentistry of New Jersey before the school was merged. She was awarded a PhD in microbiology ...

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 The Kozak consensus sequence (Kozak consensus or Kozak sequence) is a Nucleic acid sequence, nucleic acid motif that functions as the protein Translation (biology), translation initiation site in most eukaryotic Messenger RNA, mRNA transcripts. Reg ...

.”Hinnebusch, Alan., “Molecular Mechanism of Scanning and Start Codon Selection in Eukaryotes.” American Society for Microbiology Vol. 75 no. 3. (2011): 434-467. Web. 11 June 2014.

Purine Purine is a heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted puri ...

(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 initiate downstream. As a consequence, different proteins are likely to be produced.

References

{{Reflist Virology

Discovery

See also

References