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IRES-Dependent Translational Control during Virus-Induced Endoplasmic Reticulum Stress and Apoptosis.

Hanson PJ, Zhang HM, Hemida MG, Ye X, Qiu Y, Yang D - Front Microbiol (2012)

Bottom Line: Recently, a growing number of cellular genes involved in growth control, cell cycle progression and apoptosis were also found to contain one or more IRES within their long highly structured 5' UTRs.Although the molecular mechanism is not entirely understood, a number of studies have revealed that several cellular biochemical processes are responsible for the switching of translation initiation to IRES-dependent.These include the cleavage of translation initiation factors by viral and/or host proteases, phosphorylation (inactivation) of host factors for translation initiation, overproduction of homologous proteins of cap-binding protein eukaryotic initiation factors (eIF)4E, suppression of cap-binding protein eIF4E expression by specific microRNA, activation of enzymes for mRNA decapping, as well as others.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, The Institute for Heart and Lung Health, St. Paul's Hospital, University of British Columbia Vancouver, BC, Canada.

ABSTRACT
Many virus infections and stresses can induce endoplasmic reticulum (ER) stress response, a host self-defense mechanism against viral invasion and stress. During this event, viral and cellular gene expression is actively regulated and often encounters a switching of the translation initiation from cap-dependent to internal ribosome-entry sites (IRES)-dependent. This switching is largely dependent on the mRNA structure of the 5' untranslated region (5' UTR) and on the particular stress stimuli. Picornaviruses and some other viruses contain IRESs within their 5' UTR of viral genome and employ an IRES-driven mechanism for translation initiation. Recently, a growing number of cellular genes involved in growth control, cell cycle progression and apoptosis were also found to contain one or more IRES within their long highly structured 5' UTRs. These genes initiate translation usually by a cap-dependent mechanism under normal physiological conditions; however, in certain environments, such as infection, starvation, and heat shock they shift translation initiation to an IRES-dependent modality. Although the molecular mechanism is not entirely understood, a number of studies have revealed that several cellular biochemical processes are responsible for the switching of translation initiation to IRES-dependent. These include the cleavage of translation initiation factors by viral and/or host proteases, phosphorylation (inactivation) of host factors for translation initiation, overproduction of homologous proteins of cap-binding protein eukaryotic initiation factors (eIF)4E, suppression of cap-binding protein eIF4E expression by specific microRNA, activation of enzymes for mRNA decapping, as well as others. Here, we summarize the recent advances in our understanding of the molecular mechanisms for the switching of translation initiation, particularly for the proteins involved in cell survival and apoptosis in the ER stress pathways during viral infections.

No MeSH data available.


Related in: MedlinePlus

The proposed model for the switch of translation initiation from cap-dependent to IRES-dependent during picornaviral infection or other cellular stresses. Positive and negative feedback loops are indicated by plus and minus signs, respectively.
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Figure 2: The proposed model for the switch of translation initiation from cap-dependent to IRES-dependent during picornaviral infection or other cellular stresses. Positive and negative feedback loops are indicated by plus and minus signs, respectively.

Mentions: It is clear that more and more newly discovered cellular mRNAs contain IRESs and can shift translation to IRES-driven initiation during ER stress. One of the most common causes of ER stress is viral infection, which can globally shut down cap-dependent translation initiation by different mechanisms. To adapt in unfavorable stress conditions, both cell and virus (e.g., HIV) need to adjust their mode translation initiation by switching from the cap-dependent to cap-independent mechanism. As picornaviruses do not have a cap structure, its RNA translation will not be inhibited; instead it will be enhanced because more translational machinery is available due to the shut-off of global cap-dependent translation are by a number of mechanisms. During transient ER stress, the IRES-containing cellular mRNAs that responsible for cell survival/growth, such as BiP, Bcl-2, VEGF, etc., will be selectively translated by the IRES-dependent mechanism using ITAFs. This mechanism allows cells to respond rapidly to the transient changes in growth conditions and to delay apoptosis. Once the stress condition is removed, the cells will resume the normal growth. However, during prolonged or severe stress, such as in persistent infection of picornaviruses, the pro-death genes, such as Apaf-1, DAP5, CHOP, p53, etc., are also selectively translated by the same IRES-driven mechanism, allowing the cells to fine-tune their responses to cellular stress and, if conditions for cell survival are not restored, to proceed with final execution of apoptosis (Figure 2).


IRES-Dependent Translational Control during Virus-Induced Endoplasmic Reticulum Stress and Apoptosis.

Hanson PJ, Zhang HM, Hemida MG, Ye X, Qiu Y, Yang D - Front Microbiol (2012)

The proposed model for the switch of translation initiation from cap-dependent to IRES-dependent during picornaviral infection or other cellular stresses. Positive and negative feedback loops are indicated by plus and minus signs, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3307021&req=5

Figure 2: The proposed model for the switch of translation initiation from cap-dependent to IRES-dependent during picornaviral infection or other cellular stresses. Positive and negative feedback loops are indicated by plus and minus signs, respectively.
Mentions: It is clear that more and more newly discovered cellular mRNAs contain IRESs and can shift translation to IRES-driven initiation during ER stress. One of the most common causes of ER stress is viral infection, which can globally shut down cap-dependent translation initiation by different mechanisms. To adapt in unfavorable stress conditions, both cell and virus (e.g., HIV) need to adjust their mode translation initiation by switching from the cap-dependent to cap-independent mechanism. As picornaviruses do not have a cap structure, its RNA translation will not be inhibited; instead it will be enhanced because more translational machinery is available due to the shut-off of global cap-dependent translation are by a number of mechanisms. During transient ER stress, the IRES-containing cellular mRNAs that responsible for cell survival/growth, such as BiP, Bcl-2, VEGF, etc., will be selectively translated by the IRES-dependent mechanism using ITAFs. This mechanism allows cells to respond rapidly to the transient changes in growth conditions and to delay apoptosis. Once the stress condition is removed, the cells will resume the normal growth. However, during prolonged or severe stress, such as in persistent infection of picornaviruses, the pro-death genes, such as Apaf-1, DAP5, CHOP, p53, etc., are also selectively translated by the same IRES-driven mechanism, allowing the cells to fine-tune their responses to cellular stress and, if conditions for cell survival are not restored, to proceed with final execution of apoptosis (Figure 2).

Bottom Line: Recently, a growing number of cellular genes involved in growth control, cell cycle progression and apoptosis were also found to contain one or more IRES within their long highly structured 5' UTRs.Although the molecular mechanism is not entirely understood, a number of studies have revealed that several cellular biochemical processes are responsible for the switching of translation initiation to IRES-dependent.These include the cleavage of translation initiation factors by viral and/or host proteases, phosphorylation (inactivation) of host factors for translation initiation, overproduction of homologous proteins of cap-binding protein eukaryotic initiation factors (eIF)4E, suppression of cap-binding protein eIF4E expression by specific microRNA, activation of enzymes for mRNA decapping, as well as others.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, The Institute for Heart and Lung Health, St. Paul's Hospital, University of British Columbia Vancouver, BC, Canada.

ABSTRACT
Many virus infections and stresses can induce endoplasmic reticulum (ER) stress response, a host self-defense mechanism against viral invasion and stress. During this event, viral and cellular gene expression is actively regulated and often encounters a switching of the translation initiation from cap-dependent to internal ribosome-entry sites (IRES)-dependent. This switching is largely dependent on the mRNA structure of the 5' untranslated region (5' UTR) and on the particular stress stimuli. Picornaviruses and some other viruses contain IRESs within their 5' UTR of viral genome and employ an IRES-driven mechanism for translation initiation. Recently, a growing number of cellular genes involved in growth control, cell cycle progression and apoptosis were also found to contain one or more IRES within their long highly structured 5' UTRs. These genes initiate translation usually by a cap-dependent mechanism under normal physiological conditions; however, in certain environments, such as infection, starvation, and heat shock they shift translation initiation to an IRES-dependent modality. Although the molecular mechanism is not entirely understood, a number of studies have revealed that several cellular biochemical processes are responsible for the switching of translation initiation to IRES-dependent. These include the cleavage of translation initiation factors by viral and/or host proteases, phosphorylation (inactivation) of host factors for translation initiation, overproduction of homologous proteins of cap-binding protein eukaryotic initiation factors (eIF)4E, suppression of cap-binding protein eIF4E expression by specific microRNA, activation of enzymes for mRNA decapping, as well as others. Here, we summarize the recent advances in our understanding of the molecular mechanisms for the switching of translation initiation, particularly for the proteins involved in cell survival and apoptosis in the ER stress pathways during viral infections.

No MeSH data available.


Related in: MedlinePlus