Received 25 July 2002; received in revised form 11 September 2002; accepted 2 October 2002 | Marilyn Kozak
The COVID-19 Resource Centre, hosted by Elsevier, provides free information in English and Mandarin on the novel coronavirus. Elsevier grants permission to make all its COVID-19-related research available in PubMed Central and other public repositories, allowing unrestricted reuse and analysis with acknowledgment of the original source.
The review by Marilyn Kozak discusses the scanning mechanism for initiation of translation in eukaryotic mRNAs. The mechanism predicts that proximity to the 5' end plays a dominant role in identifying the start codon, leading to the 'position effect' where mutations creating an AUG codon upstream shift translation to that site. Two mechanisms, reinitiation and context-dependent leaky scanning, enable downstream AUG codons to be accessed. These mechanisms are not new but have been observed in various cases, including a plant virus mRNA initiating translation from three sites over 900 nt. Understanding these mechanisms helps explain human diseases caused by mutations affecting the expression of critical genes or hereditary thrombocythemia, where mutations remove or restructure upstream open reading frames, increasing translational efficiency and overproduction of cytokines.
The review also covers constraints imposed by the scanning mechanism, such as silent downstream cistrons, the first-AUG rule, inhibition by upstream AUG codons and secondary structures, non-AUG start codons, and context-dependent leaky scanning. It discusses the biological significance of these mechanisms and provides examples from both cellular and viral mRNAs. The review highlights the importance of the scanning mechanism in regulating gene expression and the challenges it faces in poorly designed mRNAs.The COVID-19 Resource Centre, hosted by Elsevier, provides free information in English and Mandarin on the novel coronavirus. Elsevier grants permission to make all its COVID-19-related research available in PubMed Central and other public repositories, allowing unrestricted reuse and analysis with acknowledgment of the original source.
The review by Marilyn Kozak discusses the scanning mechanism for initiation of translation in eukaryotic mRNAs. The mechanism predicts that proximity to the 5' end plays a dominant role in identifying the start codon, leading to the 'position effect' where mutations creating an AUG codon upstream shift translation to that site. Two mechanisms, reinitiation and context-dependent leaky scanning, enable downstream AUG codons to be accessed. These mechanisms are not new but have been observed in various cases, including a plant virus mRNA initiating translation from three sites over 900 nt. Understanding these mechanisms helps explain human diseases caused by mutations affecting the expression of critical genes or hereditary thrombocythemia, where mutations remove or restructure upstream open reading frames, increasing translational efficiency and overproduction of cytokines.
The review also covers constraints imposed by the scanning mechanism, such as silent downstream cistrons, the first-AUG rule, inhibition by upstream AUG codons and secondary structures, non-AUG start codons, and context-dependent leaky scanning. It discusses the biological significance of these mechanisms and provides examples from both cellular and viral mRNAs. The review highlights the importance of the scanning mechanism in regulating gene expression and the challenges it faces in poorly designed mRNAs.