8 Coupled Termination-Reinitiation Events in mRNA Translation

Abstract

Bicistronic (and polycistronic) mRNA translation is commonplace in eubacteria, although translation of the downstream cistrons may not invariably involve coupled termination-reinitiation events. In contrast, efficient translation of the downstream cistron of a bicistronic mRNA is exceedingly rare in eukaryotes, unless there is an internal ribosome entry site (IRES) or unless the upstream cistron is very short. In this chapter, we first review the eubacterial mechanism of coupled termination-reinitiation and then discuss the reasons that similar events do not generally occur in eukaryotes. We then review the mechanism underlying one of the few exceptional cases of reinitiation on a eukaryotic bicistronic mRNA with a long upstream open reading frame (ORF), and we conclude by examining what it is that is so very different when the ORF is short that it results in reinitiation being the normal (default) outcome.

TRANSLATIONAL COUPLING AND TERMINATION-REINITIATION IN PROKARYOTES
Each cistron of a eubacterial polycistronic mRNA usually has its own Shine-Dalgarno (SD) motif, which should, in principle, allow it to be translated independently. However, in a great many polycistronic mRNAs, there is translational coupling: Initiation of translation of a downstream cistron (cistron n + 1) is quite strictly dependent on translation of an upstream cistron, generally the immediate upstream cistron (cistron n). The usual explanation is that the initiation site of cistron n + 1 is occluded by secondary structure base-pairing with the coding region of cistron n (often the far upstream coding region), and so it requires translation of cistron n to unwind this secondary...