Hidden Infidelities of the Translational Stop Signal

Abstract

Publisher Summary This chapter provides evidence that there is a subtle layer of cellular regulation in which translational stop signals play a part and for which the relative strength of the signals is critical. Specific signals for the termination of protein synthesis were predicted from the studies of nonsense mutations. Such mutations were associated with the appearance of amino-terminal fragments of the affected gene products, indicating that protein synthesis had been prematurely terminated. A simultaneous investigation with the bacteriophage T4rII gene also identified UAA and UAG as translational stop codons. The historical development of ideas and discoveries related to the functioning of the genetic code has molded the perception about the translational stop signal as a triplet. However, experiments investigating the effects of the surrounding nucleotide sequence and the suppression of stop signals by suppressor or noncognate tRNAs suggested hidden infidelities in the signal. There is much evidence suggesting that the efficiency of translational stop signals can be influenced in cis by the surrounding sequence of mRNA. There are some examples of suppression of translational stop signals by naturally occurring tRNAs that may be physiologically significant. Special protein factors are involved in the recognition of translational stop signals as part of the termination machinery. Their existence was initially suggested by in vitro studies indicating a factor in cell-free extracts apart from tRNA, ribosomes, or elongation factors that influenced peptide release.