The Role of the 5′ Untranslated Region of Eukaryotic Messenger RNAs in Translation and Its Investigation Using Antisense Technologies

This chapter discusses the recent advances in the field of translational control and the possibility of applying the powerful antisense technology to investigate some of the unanswered questions, especially those pertaining to the role of the 5’untranslated region (UTR) on translation initiation. Translational regulation is predominantly exerted during the initiation phase that is considered to be the rate-limiting step. Two types of translational regulation can be distinguished: global, in which the initiation rate of (nearly) all cellular messenger RNA (mRNA) is controlled and selective, in which the translation rate of specific mRNAs varies in response to the biological stimuli. In most cases of global regulation, control is exerted via the phosphorylation state of certain initiation factors, whereas only a few examples of selective regulation have been characterized well enough to define the underlying molecular events. Interestingly, cis-acting regulatory sequences, affecting translation initiation, have been found not only in the 5’UTRs of selectively regulated mRNAs, but also in the 3’UTRs. Thus, in addition to the protein encoding open reading frames, both the 5’ and 3’UTRs of mRNAs must be considered for their effect on translation.