Cap-Independent Initiation

Some mRNAs can initiate by a cap-independent process. In this type of initiation the ribosome is guided to the correct initiation codon by structural motifs in the 5’-untranslated region of the mRNA. These motifs are usually referred to as internal ribosome entry sites (IRES). During cap-independent initiation, the activated 40S subunit recognises a structural motif in the 5’-UTR of the mRNA. The subunits bind at or close to the identified structural elements and presumably scans the mRNA sequence from the ribosome binding site to the initiator codon. Cap-independent initiation requires additional proteins such as the La-protein (a polypyrimidine-binding protein, PTB) that bind to a polypyrimidine containing sequence in the mRNA (a sequence containing an unusually high percentage of pyrimidines i.e. uridines and cytosines).