Translation initiation by the hepatitis C virus IRES requires eIF1A and ribosomal complex remodeling

Jaafar, Zane A.; Oguro, Ami; Nakamura, Yoshikazu; Kieft, Jeffrey

doi:10.7554/elife.21198

Cited by 48 publications

(61 citation statements)

References 78 publications

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“…Its prokaryotic orthologue, IF2, is also involved in the delivery of the initiator fMet-tRNA i fMet . This suggests that the eIF3/eIF5B prokaryotic-like mechanism of initiation that was already described for the hepatitis C virus IRES (Jaafar et al, 2016; Terenin et al, 2008) may play a role during chronic ISR, which warrants further investigation.…”

Section: Discussionmentioning

confidence: 56%

A Unique ISR Program Determines Cellular Responses to Chronic Stress

et al. 2017

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SUMMARY Integrated Stress Response is a homeostatic mechanism induced by endoplasmic reticulum (ER) stress. In acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by normalization of protein synthesis. Here, we report a dramatically different response during chronic ER stress. This chronic ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis. The program includes PERK-dependent switching to an eIF3-dependent translation initiation mechanism resulting in partial but not complete translational recovery, which, together with transcriptional reprogramming, selectively bolsters expression of proteins with ER functions. Coordination of transcriptional and translational reprogramming prevents ER dysfunction and inhibits “foamy cell” development, thus establishing a molecular basis for understanding human diseases associated with ER dysfunction.

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Section: Discussionmentioning

confidence: 56%

A Unique ISR Program Determines Cellular Responses to Chronic Stress

et al. 2017

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“…Binding of eIF2-Met-tRNA i Met to preinitiation complexes is facilitated by the eIF3 subunit eIF3a [155]. Efficient 48S initiation complex formation also requires eIF1A, whereas eIF1 interferes with 48S initiation complex formation [165,179]. Domain II of HCV-like IRESs stimulates eIF5-mediated hydrolysis of eIF2-bound GTP and joining of the 60S subunit [141,164,165].…”

Section: Steps Involved In Hcv Translation Initiationmentioning

confidence: 99%

Hepatitis C Virus Translation Regulation

Niepmann

Gerresheim

2020

IJMS

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Translation of the hepatitis C virus (HCV) RNA genome is regulated by the internal ribosome entry site (IRES), located in the 5’-untranslated region (5′UTR) and part of the core protein coding sequence, and by the 3′UTR. The 5′UTR has some highly conserved structural regions, while others can assume different conformations. The IRES can bind to the ribosomal 40S subunit with high affinity without any other factors. Nevertheless, IRES activity is modulated by additional cis sequences in the viral genome, including the 3′UTR and the cis-acting replication element (CRE). Canonical translation initiation factors (eIFs) are involved in HCV translation initiation, including eIF3, eIF2, eIF1A, eIF5, and eIF5B. Alternatively, under stress conditions and limited eIF2-Met-tRNAiMet availability, alternative initiation factors such as eIF2D, eIF2A, and eIF5B can substitute for eIF2 to allow HCV translation even when cellular mRNA translation is downregulated. In addition, several IRES trans-acting factors (ITAFs) modulate IRES activity by building large networks of RNA-protein and protein–protein interactions, also connecting 5′- and 3′-ends of the viral RNA. Moreover, some ITAFs can act as RNA chaperones that help to position the viral AUG start codon in the ribosomal 40S subunit entry channel. Finally, the liver-specific microRNA-122 (miR-122) stimulates HCV IRES-dependent translation, most likely by stabilizing a certain structure of the IRES that is required for initiation.

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“…Translation initiation mediated by HCV IRES is a sequential process that requires three main distinct steps that lead to formation of stable PIC . Although this ordered process has been observed, multiple alternative pathways coexists, to circumvent inactivated eIF2 during stress conditions, elevated Mg 2+ concentration or minimal factor pathways (eIF3/eIF5B, eIF2A, or eIF2D) . One of these pathways requires eIF1a .…”

Section: Viral Ires Classificationmentioning

confidence: 99%

“…[151][152][153][154][155][156] One of these pathways requires eIF1a. 156 cloverleaf structure (CL) is involved in viral replication (light green). Nucleotides that are critical for IRES activity or that are required for specific trans-acting factor recruitments are shown in orange.…”

Section: The Hcv Ires Mode Of Actionmentioning

confidence: 99%

Viral internal ribosomal entry sites: four classes for one goal

2017

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To ensure efficient propagation, viruses need to rapidly produce viral proteins after cell entrance. Since viral genomes do not encode any components of the protein biosynthesis machinery, viral proteins must be produced by the host cell. To hi-jack the host cellular translation, viruses use a great variety of distinct strategies. Many single-stranded positive-sensed RNA viruses contain so-called internal ribosome entry sites (IRESs). IRESs are structural RNA motifs that have evolved to specific folds that recruit the host ribosomes on the viral coding sequences in order to synthesize viral proteins. In host canonical translation, recruitment of the translation machinery components is essentially guided by the 5' cap (m G) of mRNA. In contrast, IRESs are able to promote efficient ribosome assembly internally and in cap-independent manner. IRESs have been categorized into four classes, based on their length, nucleotide sequence, secondary and tertiary structures, as well as their mode of action. Classes I and II require the assistance of cellular auxiliary factors, the eukaryotic intiation factors (eIF), for efficient ribosome assembly. Class III IRESs require only a subset of eIFs whereas Class IV, which are the more compact, can promote translation without any eIFs. Extensive functional and structural investigations of IRESs over the past decades have allowed a better understanding of their mode of action for viral translation. Because viral translation has a pivotal role in the infectious program, IRESs are therefore attractive targets for therapeutic purposes. WIREs RNA 2018, 9:e1458. doi: 10.1002/wrna.1458 This article is categorized under: Translation > Ribosome Structure/Function Translation > Translation Mechanisms RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.

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Translation initiation by the hepatitis C virus IRES requires eIF1A and ribosomal complex remodeling

Cited by 48 publications

References 78 publications

A Unique ISR Program Determines Cellular Responses to Chronic Stress

A Unique ISR Program Determines Cellular Responses to Chronic Stress

Hepatitis C Virus Translation Regulation

Viral internal ribosomal entry sites: four classes for one goal

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