Trends in Microbiology
ReviewRegulation Mechanisms of Viral IRES-Driven Translation
Section snippets
Viruses Take Advantage of IRESs in Host Cells
Due to limited coding capacity in their genomes, viruses have evolved various ways to hijack key steps in the cellular gene expression pathway, among which the commandeering of translation processes can arguably be considered a critical step for viral propagation [1]. Based on the mechanism of translation initiation, which also serves as the rate-limiting step, cellular translation pathways can be divided into cap- and IRES-dependent translation [2]. In eukaryotes, protein-coding messenger RNAs
Viral Manipulation of Cap-Dependent Translation
Prior to discussing how RNA viruses initiate IRES-dependent translation, it is necessary to compare the differences and interconnections between the two translation mechanisms described. Cap-dependent translation can be divided into four steps: initiation, elongation, termination, and ribosome recycling, with each step mediated by a distinct set of regulatory factors. Given its importance as the rate-limiting step, the initiation mechanism has been extensively studied (reviewed in [10]), and
Viral Utilization of IRES-Dependent Translation
The IRES element was first identified in the late 1980s from the 5ʹ-UTR of the poliovirus (PV) and encephalomyocarditis virus (EMCV) genomes; both viruses are members of the picornavirus family 7, 8. Since then IRES elements have been shown to exist in all genera of Picornaviridae [15]. Besides RNA viruses, IRES elements have also been widely identified in other viruses (retroviruses and DNA viruses etc.) as well as cellular mRNAs 3, 6, 16, 17. However, the structure and function of cellular
ITAF Modulation of IRES-Mediated Translation during Infection
Instead of binding to ribosome directly, not all of viral IRESs were able to drive translation properly in rabbit reticulate lysates, but this was resolved after human cell lysates were supplemented, indicating the critical role of cellular proteins to the regulation of IRES activity. Since PTB and La were identified as ITAFs 76, 77, many proposed ITAFs have been reported (Table 1). Most, if not all, of these ITAFs are RNA-processing factors containing multiple copies of RNA-binding domains 3, 4
Concluding Remarks and Future Perspectives
In this review, we presented the latest understanding regarding the mechanisms involved in viral IRES-driven translation. The inherent structure-based properties of the IRESs suggest that these elements can serve as ideal platforms for the development of antiviral drugs [52]. Antisense nucleotides specifically targeting IRES elements have been developed, but issues of inefficient delivery and off-target effects remain to be overcome [9]. However, other ways of utilizing the IRES for viral
Acknowledgments
Due to the limitation of length, the authors apologize to those colleagues whose work could not be cited. This work was financially supported by a grantfrom the Chang Gung Memorial Hospital (CMRPD1D0313), Taoyuan, Taiwan.
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These authors contributed equally to this work.