Protein synthesis is one of the most complex cellular processes, involving
numerous translation components that interact in multiple sequential steps.
The most complex stage in protein synthesis is the initiation process. It
involves initiation factor-mediated assembly of a 40S ribosomal subunit and
initiator tRNA into a 48S initiation complex at the initiation codon of an
mRNA and subsequent joining of a 60S ribosomal subunit to form a translati
onally active 80S ribosome. The basal set of factors required for translati
on initiation has been determined, and biochemical, genetic, and structural
studies are now beginning to reveal details of their individual functions
in this process. The mechanism of translation initiation has also been foun
d to be influenced significantly by structural properties of the 5' and 3'
termini of individual mRNAs. This review describes some of the major develo
pments in elucidating molecular details of the mechanism of initiation that
have occurred over the last decade.