How Retroviruses Escape the Nonsense-Mediated mRNA Decay

Mocquet, Vincent; DurandSebastien,; JalinotPierre,

doi:10.1089/aid.2014.0326

Cited by 19 publications

(16 citation statements)

References 133 publications

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“…It is also possible that specific sequences in these conserved uORF are critical for triggering NMD. In mammals, only a small fraction of mRNAs with uORFs are downregulated by NMD [16, 154, 155] and thus a future area of investigation is to determine what distinguishes NMD-inducing uORFs from non-NMD-inducing uORFs.…”

Section: Nmd In Stress Responses In Plantsmentioning

confidence: 99%

Stress and the nonsense-mediated RNA decay pathway

Goetz

Wilkinson

2017

Cell. Mol. Life Sci.

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Cells respond to internal and external cellular stressors by activating stress response pathways that re-establish homeostasis. If homeostasis is not achieved in a timely manner, stress pathways trigger programmed cell death (apoptosis) to preserve organism integrity. A highly-conserved stress pathway is the unfolded protein response (UPR), which senses excessive amounts of unfolded proteins in the ER. While a physiologically beneficial pathway, the UPR requires tight regulation to provide a beneficial outcome and avoid deleterious consequences. Recent work has demonstrated that a conserved and highly selective RNA degradation pathway—Nonsense-Mediated RNA Decay (NMD)—serves as a major regulator of the UPR pathway. NMD degrades mRNAs encoding UPR components to prevent UPR activation in response to innocuous ER stress. In response to strong ER stress, NMD is inhibited by the UPR to allow for a full-magnitude UPR response. Recent studies have indicated that NMD also has other stress-related functions, including promoting the timely termination of the UPR to avoid apoptosis; NMD also regulates responses to non-ER stressors, including hypoxia, amino-acid deprivation, and pathogen infection. NMD regulates stress responses in species across the phylogenetic scale, suggesting it has conserved roles in shaping stress responses. Stress pathways are frequently constitutively activated or dysregulated in human disease, raising the possibility that “NMD therapy” may provide clinical benefit by downmodulating stress responses.

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Section: Nmd In Stress Responses In Plantsmentioning

confidence: 99%

Stress and the nonsense-mediated RNA decay pathway

Goetz

Wilkinson

2017

Cell. Mol. Life Sci.

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“…The overall sensitivity of HTLV-1 retroviral RNA to NMD has been known for a few years [42,43]. Although the molecular determinants of RNA features triggering NMD sensitivity have not yet been clearly defined [78], we can at least suggest that this sensitivity may have multiple origins; the viral RNA can be directly as well as indirectly targeted by the NMD machinery. Direct regulation: As described above, the half-life of unspliced HTLV-1 RNA is increased under NMD inhibition.…”

Section: Htlv-1 Viral Mrna Exhibits Nmd-initiating Featuresmentioning

confidence: 95%

The Complex Relationship between HTLV-1 and Nonsense-Mediated mRNA Decay (NMD)

2020

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Before the establishment of an adaptive immune response, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defense mechanisms are debated. Among these mechanisms, we focused on an RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as has been recently demonstrated. NMD is a co-translational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition. HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the fittest clones despite genome instability; however, its direct long-term impact remains to be investigated.

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“…The overall sensitivity of HTLV-1 retroviral RNA to NMD has been known for a few years [57,58]. However, the molecular determinants or RNA features triggering NMD sensitivity have not yet been clearly defined [112]. Additional work is needed to identify which stop codons are the most likely to induce NMD.…”

Section: Htlv-1 Viral Mrna Exhibits Nmd-initiating Featuresmentioning

confidence: 99%

An Antiviral Process Targeting HTLV-1: The Complex Relationship between HTLV-1 and Nonsense-mediated mRNA Decay

Prochasson¹,

Jalinot²,

Mocquet³

2020

Preprint

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Before the adaptive immune response is established, retroviruses can be targeted by several cellular host factors at different stages of the viral replication cycle. This intrinsic immunity relies on a large diversity of antiviral processes. In the case of HTLV-1 infection, these active innate host defence mechanisms are debated. Among these mechanisms, we focused on a RNA decay pathway called nonsense-mediated mRNA decay (NMD), which can target multiple viral RNAs, including HTLV-1 unspliced RNA, as it has been recently demonstrated. NMD is a cotranslational process that depends on the RNA helicase UPF1 and regulates the expression of multiple types of host mRNAs. RNA sensitivity to NMD depends on mRNA organization and the ribonucleoprotein (mRNP) composition.HTLV-1 has evolved several means to evade the NMD threat, leading to NMD inhibition. In the early steps of infection, NMD inhibition favours the production of HTLV-1 infectious particles, which may contribute to the survival of the most fit clones despite genome instability; however, its direct longterm impact remains to be investigated.

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How Retroviruses Escape the Nonsense-Mediated mRNA Decay

Cited by 19 publications

References 133 publications

Stress and the nonsense-mediated RNA decay pathway

Stress and the nonsense-mediated RNA decay pathway

The Complex Relationship between HTLV-1 and Nonsense-Mediated mRNA Decay (NMD)

An Antiviral Process Targeting HTLV-1: The Complex Relationship between HTLV-1 and Nonsense-mediated mRNA Decay

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