Internal ribosome entry sites in eukaryotic mRNA molecules
- Christopher U.T. Hellen1,3 and
- Peter Sarnow2,3
- 1Department of Microbiology and Immunology, Morse Institute for Molecular Genetics, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203, USA; 2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA
This extract was created in the absence of an abstract.
Initiation of translation of most eukaryotic mRNAs commences with 5′ end–dependent recruitment of 40S ribosomal subunits to the mRNA. The 40S subunit carrying the initiator methionine-tRNA and certain eukaryotic initiation factors (eIFs) is thought to scan the mRNA in a 5′ to 3′ direction until an appropriate start codon is encountered at which stage a 60S subunit joins to form an 80S ribosome that can decode the RNA into protein (Kozak 1989; Hershey and Merrick 2000). A subset of mRNAs contains internal ribosomal entry sites (IRESs), usually in the 5′ NTR, that enable end-independent initiation to occur. IRES-containing mRNAs are not subjected to many of the regulatory mechanisms that control recruitment of most mRNAs to the translation apparatus. In this review, we briefly provide an introduction to the known mechanisms of translation initiation. Then, we discuss in detail the molecular mechanisms of IRES-mediated initiation and how they are used by specific mRNAs to permit translation under physiological circumstances such as mitosis, apoptosis, hypoxia, and some viral infections when translation of most mRNAs is repressed.
Mechanisms that mediate translation initiation
Most vertebrate mRNAs are functionally monocistronic and contain a 5′-terminal m7GpppN (where N can be any nucleotide) cap structure. The initiation codon used as the start site for protein synthesis is preceded by a 5′ nontranslated region (NTR) in which length, nucleotide composition, and structure can determine the efficiency and the mechanism by which a given mRNA is translated (Hershey and Merrick 2000). For the most part, the factors that influence the binding of 40S subunits to the mRNA provide the limiting step in translation initiation. In recent years, it has been found that a particular initiation mechanism can be used preferentially when one or more specific initiation factors are limiting. Thus, it is crucial to the understanding of translational regulation to know …
