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POLAR EFFECTS ON GENE EXPRESSION

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Some mutations that affect the expression of a gene in a polycistronic mRNA can have secondary effects on the transcription of downstream genes. Such mutations are said to exert a polar effect on gene expression. Several types of mutations can result in polar effects. One type of mutation that can cause a polar effect is an insertion mutation that carries a factor-independent transcriptional terminator. For example, if a transposon “hops” into a polycistronic transcription unit, the transcriptional terminators on the transposon may prevent the transcription of genes downstream of the insertion site in the same polycistronic transcription unit. Likewise, a “knockout” of a gene by insertion of an antibiotic resistance gene with a transcriptional terminator causes a polar effect on the genes downstream in the same transcription unit.

A second way a mutation in an upstream coding sequence can affect transcription of a downstream coding sequence is through effects on ρ-dependent termination of transcription. Recall that translation of mRNAs in bacteria normally occurs simultaneously with transcription and that the mRNA is translated in the same 5′-to-3′ direction as it is synthesized. Moreover, ribosomes often load onto a TIR as soon as it is vacated by the preceding ribosome, so that the mRNA is coated with translating ribosomes. If a nonsense mutation causes premature dissociation of ribosomes, the abnormally naked mRNA downstream of the mutation may be targeted by the transcription termination factor ρ, which may find an exposed rut sequence in the mRNA and cause transcription termination, as shown in Figures 2.15 and 2.36. The nonsense mutation therefore prevents the expression of the downstream gene by preventing its transcription. Such ρ-dependent polarity effects occur only if a rut sequence recognizable by ρ and a ρ-dependent terminator lie between the point of the mutation and the next downstream TIR.


Figure 2.35 Model for translational coupling in a polycistronic mRNA. (A) The secondary structure of the RNA sequesters the translational initiation region (TIR) of the second coding sequence (Gene 2) and blocks translation initiation (note that the Shine-Dalgarno shown is not the complete consensus sequence). (B) Translation of the first coding sequence (Gene 1) results in disruption of the secondary structure, allowing a ribosome to access the TIR of Gene 2 to translate the second coding sequence.

Superficially, translational coupling and polarity due to transcription termination have similar effects; in both cases, blocking the translation of one coding sequence affects the synthesis of another polypeptide encoded downstream on the same mRNA. However, the molecular bases of the two phenomena are completely different.

Snyder and Champness Molecular Genetics of Bacteria

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