UGA: a dual signal for 'stop' and for recoding in protein synthesis

UGA remains an enigma as a signal in protein synthesis. Long recognized as a stop signal that is prone to failure when under competition from near cognate events, there was growing belief that there might be functional significance in the production of small amounts of extended proteins. This view has been reinforced with the discovery that UGA is found at some recoding sites where frameshifting occurs as a regulatory mechanism for controlling the gene expression of specific proteins, and it also serves as the code for selenocysteine (Sec), the 21st amino acid. Why does UGA among the stop signals play this role specifically, and how does it escape being used to stop protein synthesis efficiently at recoding sites involving Sec incorporation or shifts to a new translational frame? These issues concerning the UGA stop signals are discussed in this review.