11 Translation Termination: It’s Not the End of the Story

Abstract

The protein synthesis apparatus must carry out translation initiation, elongation, and termination to synthesize a complete protein product. Each step of this process has evolved to occur with great accuracy and can be utilized to regulate gene expression. Until relatively recently, however, translation termination was the least investigated and understood aspect of the translation process. Recent results, however, suggest that translation termination also can be used to modulate gene expression. The fact that sequences in the 3′-untranslated regions (3′UTRs) of mRNAs bind to RNA-binding proteins and can dramatically affect the translation initiation process suggests that steps which occur at translation termination may strongly affect subsequent events in the translation process. It is conceivable that translation termination may be involved in determining whether ribosomes reinitiate at the translation start site of the same transcript for subsequent rounds of translation.

In recent years, there has been a significant advancement in our knowledge of the translation termination process. The goal of this short review is to describe the state of knowledge concerning the mechanism of translation termination. Results from studies using both prokaryotic and eukaryotic systems are discussed. In particular, we attempt to address the potential role of the translation termination process in the regulation of gene expression. In addition, we discuss the modulation of the termination process as a potential target to treat diseases that arise as a consequence of mutations that prematurely terminate translation.

GENERAL PRINCIPLES OF TRANSLATION TERMINATION
Nearly 40 years ago, Crick and colleagues deduced the “general nature of...