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Chapter 12 : Souvenirs from My Genetic Initiation

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Souvenirs from My Genetic Initiation, Page 1 of 2

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Abstract:

In this chapter the author talks about his experience in John Roth’s lab. The author chose to study , a frameshift suppressor isolated by Hiko Kohno in the lab. Frameshift suppressors are mutant tRNAs that acquire the ability or read four-letter codons and thus can correct mutations caused by single base additions in the message (+1 frameshifts). The two tRNAs have nearly identical anticodon arm sequences, and they both carry two pseudouridine modifications at corresponding positions. Thus, it seemed likely that tRNA would be similarly impaired by inactivation. The idea fit nicely into the shaping up model for regulation, as one predicted that the tRNA defect would slow down translation in the leader RNA and thus account for derepression. At weakly suppressed sites, the presence of a mutation eliminated suppression completely. This suggested that the efficiency with which tRNA read the UAG codon was influenced by the sequence surrounding the codon in the messenger RNA: the codon context. It was proposed that impairs the function of the tRNA reading the codon next to ACC at the site (a leucine tRNA that does contain pseudouridine), thus favoring frame-shifting activity.

Citation: Bossi L. 2011. Souvenirs from My Genetic Initiation, p 117-122. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch12

Key Concept Ranking

Frameshift Mutation
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DNA Sequencing Methods
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FIGURE 1

Comparison of anticodon arm sequences of tRNA and tRNA. A mutation in tRNA restoring basal levels of operon expression in a mutant background is indicated.

Citation: Bossi L. 2011. Souvenirs from My Genetic Initiation, p 117-122. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch12
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References

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1. Ames, B. N.,, T. H. Tsang,, M. Buck, and , M. F. Christman. 1983. The leader mRNA of the histidine attenuator region resembles tRNAHis: possible general regulatory implications. Proc. Natl. Acad. Sci. USA 80: 52405242.
2. Barnes, W. M. 1978. DNA sequence from the histidine operon control region: seven histidine codons in a row. Proc. Natl. Acad. Sci. USA 75:42814285.
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5. Bossi, L.,, T. Kohno, and , J. R. Roth. 1983. Genetic characterization of the sufj frameshift suppressor in Salmonella typhimurium. Genetics 103:3142.
6. Bossi, L., and , J. R. Roth. 1981. Four–base codons ACCA, ACCU and ACCC are recognized by frameshift suppressor sufJ. Cell 25:489496.
7. Bossi, L., and , J. R. Roth. 1980. The influence of codon context on genetic code translation. Nature 286:123127.
8. Bossi, L., and , D. M. Smith. 1984. Suppressor sufJ: a novel type of tRNA mutant that induces translational frameshifting. Proc. Natl. Acad. Sci. USA 81:61056109.
9. Johnston, H.,, W. Barnes,, F. Chumley,, L. Bossi, and , J. Roth. 1980. Model for regulation of the histidine operon of Salmonella. Proc. Natl. Acad. Sci. USA 77:508512.
10. Johnston, H., and , J. Roth. 1981. DNA sequence changes of mutations altering attenuation control of the histidine operon of Salmonella typhimurium. J. Mol. Biol. 145:735756.
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12. Roth, J. R. 1981. Frameshift suppression. Cell 24:601602.

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