Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein

Cáceres, C. Joaquín; Angulo, Jenniffer; Lowy, Fernando; Contreras, Nataly; Walters, Beth; Olivares, Eduardo; Allouche, Delphine; Merviel, Anne; Pino, Karla; Sargueil, Bruno; Thompson, Sunnie R.; López-Lastra, Marcelo

doi:10.1093/nar/gky1249

Cited by 9 publications

(1 citation statement)

References 67 publications

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“…Second, eIF5A1 is required for the function of the viral trans-activator protein Rex which is necessary for the expression of structural proteins of human T-cell leukemia virus type I [99]. Additionally, eIF5A1 is involved in both internal ribosome entry site (IRES)mediated HIV-1 RNA translation and cap-dependent RNA translation [100], and inhibition of hypusine formation impairs the IRES-mediated translation initiation at several retroviral IRESs [101,102]. For Ebola virus (EBOV), blocking of hypusine formation inhibited EBOV gene expression and decreased the expression level of hexameric zinc-finger protein VP30, an essential component of the viral polymerase [103].…”

Section: Roles Of Eif5a1 In Other Diseases Viral Infectionsmentioning

confidence: 99%

Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease

Lau

2020

Cancer Cell Int

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The eukaryotic translation initiation factor 5A1 (eIF5A1) and its homolog eIF5A2 are the only two human proteins containing the unique post-translational modification-hypusination, which is essential for the function of these two proteins. eIF5A1 was initially identified as a translation initiation factor by promoting the first peptide bond formation of protein during translation; however, recent results suggest that eIF5A1 also functions as a translation elongation factor. It has been shown that eIF5A1 is implicated in certain human diseases, including diabetes, several human cancer types, viral infections and diseases of neural system. Meanwhile, eIF5A2 is overexpressed in many cancers, and plays an important role in the development and progression of cancers. As multiple roles of these two factors were observed among these studies, therefore, it remains unclear whether they act as oncogene or tumor suppressor. In this review, the recent literature of eIF5As and their roles in human diseases, especially in human cancers, will be discussed.

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Section: Roles Of Eif5a1 In Other Diseases Viral Infectionsmentioning

confidence: 99%

Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease

Lau

2020

Cancer Cell Int

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Post-translational modifications of hnRNP A1 differentially modulate retroviral IRES-mediated translation initiation

Barrera

Ramos

Vera-Otárola

et al. 2020

Nucleic Acids Research

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The full-length mRNAs of the human immunodeficiency virus type-1 (HIV-1), the human T-cell lymphotropic virus type-1 (HTLV-1), and the mouse mammary tumor virus (MMTV) harbor IRESs. The activity of the retroviral-IRESs requires IRES-transacting factors (ITAFs), being hnRNP A1, a known ITAF for the HIV-1 IRES. In this study, we show that hnRNP A1 is also an ITAF for the HTLV-1 and MMTV IRESs. The MMTV IRES proved to be more responsive to hnRNP A1 than either the HTLV-1 or the HIV-1 IRESs. The impact of post-translational modifications of hnRNP A1 on HIV-1, HTLV-1 and MMTV IRES activity was also assessed. Results show that the HIV-1 and HTLV-1 IRESs were equally responsive to hnRNP A1 and its phosphorylation mutants S4A/S6A, S4D/S6D and S199A/D. However, the S4D/S6D mutant stimulated the activity from the MMTV-IRES to levels significantly higher than the wild type hnRNP A1. PRMT5-induced symmetrical di-methylation of arginine residues of hnRNP A1 enabled the ITAF to stimulate the HIV-1 and HTLV-1 IRESs while reducing the stimulatory ability of the ITAF over the MMTV IRES. We conclude that retroviral IRES activity is not only dependent on the recruited ITAFs but also relies on how these proteins are modified at the post-translational level.

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The double-stranded RNA-binding protein, Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation

Ramos

Monette

Niu

et al. 2021

Nucleic Acids Research

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Translation initiation of the viral genomic mRNA (vRNA) of human immunodeficiency virus-type 1 (HIV-1) can be mediated by a cap- or an internal ribosome entry site (IRES)-dependent mechanism. A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5’untranslated region (5′UTR) of the HIV-1 vRNA and promotes its cap-dependent translation. In this study, we now evaluate the role of Staufen1 as an HIV-1 IRES-transacting factor (ITAF). We first confirm that Staufen1 associates with both the HIV-1 vRNA and the Gag protein during HIV-1 replication. We found that in HIV-1-expressing cells, siRNA-mediated depletion of Staufen1 reduces HIV-1 vRNA translation. Using dual-luciferase bicistronic mRNAs, we show that the siRNA-mediated depletion and cDNA-mediated overexpression of Staufen1 acutely regulates HIV-1 IRES activity. Furthermore, we show that Staufen1-vRNA interaction is required for the enhancement of HIV-1 IRES activity. Interestingly, we find that only Staufen1 harboring an intact dsRNA-binding domain 3 (dsRBD3) rescues HIV-1 IRES activity in Staufen1 CRISPR-Cas9 gene edited cells. Finally, we show that the expression of Staufen1-dsRBD3 alone enhances HIV-1 IRES activity. This study provides evidence of a novel role for Staufen1 as an ITAF promoting HIV-1 vRNA IRES activity.

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Non-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein

Cited by 9 publications

References 67 publications

Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease

Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease

Post-translational modifications of hnRNP A1 differentially modulate retroviral IRES-mediated translation initiation

The double-stranded RNA-binding protein, Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation

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