Initiation Factors Which Recognize mRNA

Abstract

A number of discoveries in the last few years have added new and clarifying information to the interpretation of events in eukaryotic protein synthesis initiation (Jagus et al., 1981). Of those discoveries, perhaps the most notable are those that relate to the binding of mRNA to 40S ribosomal subunits as this area had generated only limited information on the mRNA recognition process and often there appeared to be conflicting reports on the specific properties of given initiation factors, especially eIF-3 and eIF-4B. Several independent lines of research have subsequently generated substantial clarification. The first line was the development of an assay by Shatkin and co-workers to identify those proteins which appeared to specifically recognize the m⁷GDP cap structure of eukaryotic rRNAs (Sonenberg & Shatkin, 1977; Sonenberg et al., 1978). A separate methodology developed by Marilyn Kozak has probed the ATP requirement for the binding of mRNA to 40S subunits. Her conclusion from these studies was that there are two ATP-dependent steps, one in which an area of the mRNA near the cap structure is bound to the 40S ribosomal subunit and a second step where the mRNA is “scanned” to locate the initiating AUG codon (Kozak, 1978; Kozak, 1980a; Kozak, 1980b).