Insights into Structural and Mechanistic Features of Viral IRES Elements.

Encarnacion Martinez-Salas,Rosario Francisco-Velilla,Javier Fernandez-Chamorro,Azman M Embarek

doi:10.3389/fmicb.2017.02629

Abstract

Internal ribosome entry site (IRES) elements are cis-acting RNA regions that promote internal initiation of protein synthesis using cap-independent mechanisms. However, distinct types of IRES elements present in the genome of various RNA viruses perform the same function despite lacking conservation of sequence and secondary RNA structure. Likewise, IRES elements differ in host factor requirement to recruit the ribosomal subunits. In spite of this diversity, evolutionarily conserved motifs in each family of RNA viruses preserve sequences impacting on RNA structure and RNA–protein interactions important for IRES activity. Indeed, IRES elements adopting remarkable different structural organizations contain RNA structural motifs that play an essential role in recruiting ribosomes, initiation factors and/or RNA-binding proteins using different mechanisms. Therefore, given that a universal IRES motif remains elusive, it is critical to understand how diverse structural motifs deliver functions relevant for IRES activity. This will be useful for understanding the molecular mechanisms beyond cap-independent translation, as well as the evolutionary history of these regulatory elements. Moreover, it could improve the accuracy to predict IRES-like motifs hidden in genome sequences. This review summarizes recent advances on the diversity and biological relevance of RNA structural motifs for viral IRES elements.

Highlights

Regulation of protein synthesis is a key step of gene expression in all organisms
The vast majority of mRNAs initiate translation by a cap-dependent mechanism (Hinnebusch, 2014). This general mechanism depends on the recognition of the m7G(5 )ppp(5 )N structure placed at the 5 end of most mRNAs (Figure 1A) by the translation eukaryotic initiation factor-4F, which is composed of three polypeptides
Inhibiting activity of the later enzyme, and eIF5A hypusination, reduces human immunodeficiency virus 1 (HIV-1) Internal ribosome entry site (IRES) activity, and translation initiation mediated by 5 untranslated region (UTR) of the human T-cell lymphotropic virus type 1 (HTLV-1) and the mouse mammary tumor virus (MMTV) mRNAs

Summary

Introduction

Regulation of protein synthesis is a key step of gene expression in all organisms. The process of RNA translation occurs in four basic steps, initiation, elongation, termination, and ribosome recycling. A recent study reported the requirement of the 40S ribosomal protein receptor of activated protein kinase C 1 (RACK1) for both, the IGR of CrPV and HCV IRES-dependent translation (Majzoub et al, 2014), this protein maps to different sites on 80S ribosome complexes assembled with CrPV or HCV IRES elements.

Results

Conclusion