Translational coupling of neighboring genes in prokaryotes

Prokaryotic genomes are gene-dense, so genes in the same orientation are often separated by short intergenic sequences or even overlap. Many mechanisms of regulation depend on open reading frames (ORFs) being spatially close to one another. Here, we describe one such mechanism, translational coupling, where translation of one gene promotes translation of a co-oriented neighboring gene. Translational coupling has been observed across the prokaryotic kingdom. Coupling is most efficient when the intergenic distance between ORFs is small. Coupling efficiency is influenced by RNA secondary structure, the presence of a Shine-Dalgarno (SD) sequence, and potentially by other cis-acting elements. While the mechanism of translational coupling has not been firmly established, two models have been proposed. In the RNA unfolding model, translation of the upstream gene in a pair disrupts inhibitory RNA secondary structure around the start codon of the downstream gene. Alternatively, the reinitiation model proposes that the same ribosome-either the 30S or complete 70S-translates both genes in a coupled pair. We describe evidence in support of each model, and we discuss the functional implications of translational coupling.