Internal ribosome entry sites in eukaryotic mRNA molecules.

By C. Hellen, P. Sarnow. Genes & Development, 2001

1,024 citations recorded by the source corpus.

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.

Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f623bc96eda3f90340f8b1afbb6d20489c597733

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

1. M. Kozak
2. Nahum Sonenberg
3. C. Bramham
4. D. Wells

In Molecular Biology

1. M. Kozak
2. Nahum Sonenberg
3. M. Holcik
4. C. Bramham
5. D. Wells
6. David M. Sabatini
7. M. Karin
8. A. Budanov

Citations in the corpus

• Pushing the limits of the scanning mechanism for initiation of translation (2002, neutral): “Rather than attempting to summarize the extensive literature on internal initiation, I refer the reader to other detailed reviews on that subject (Dever, 2002; Hellen and Sarnow, 2001; Pestova et al., 2001).”
• Gene-specific regulation by general translation factors. (2002, neutral): “This eIF2 Phosphorylation alternate mechanism has been reported for several viral Phosphorylation of eIF2 does not directly impair eIF2 mRNAs including those from poliovirus, EMCV, and hep- function, but indirectly affects guanine nucleotide exatitis C virus ( Hellen and Sarnow, 2001 ).”
• A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. (2008, background): “Many of these IRES-containing mRNAs are regulated during stress situations such as differentiation or apoptosis (Hellen and Sarnow 2001; Holcik and Sonenberg 2005).”
• Translational control in stress and apoptosis (2005, background): “It is likely that most of these mRNAs contain an INTERNAL RIBOSOME-ENTRY SITE (IRES) in their 5′ UTR, as IRES-mediated translation is the only validated cap-independent translational mechanis”
• Regulation of translation via mRNA structure in prokaryotes and eukaryotes. (2005, background): “Similar claims about a putative IRES from cricket paralysis virus (Hellen and Sarnow, 2001) are called into question by a recent study in which IRES activity, assayed via synthetic dicistronic constructs, and actual virus replication were tested in a range of insect cell lines.”