Emerging Roles of m7G-Cap Hypermethylation and Nuclear Cap-Binding Proteins in Bypassing Suppression of eIF4E-Dependent Translation
Translation regulation is essential to the survival of hosts. Most translation initiation falls under the control of the mTOR pathway, which regulates protein production from mono-methyl-guanosine (m7G) cap mRNAs. However, mTOR does not regulate all translation; hosts and viruses alike employ altern...
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2025-03-01
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| author | Kathleen Boris-Lawrie Jessica Liebau Abdullgadir Hayir Xiao Heng |
| author_facet | Kathleen Boris-Lawrie Jessica Liebau Abdullgadir Hayir Xiao Heng |
| author_sort | Kathleen Boris-Lawrie |
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| description | Translation regulation is essential to the survival of hosts. Most translation initiation falls under the control of the mTOR pathway, which regulates protein production from mono-methyl-guanosine (m7G) cap mRNAs. However, mTOR does not regulate all translation; hosts and viruses alike employ alternative pathways, protein factors, and internal ribosome entry sites to bypass mTOR. Trimethylguanosine (TMG)-caps arise from hypermethylation of pre-existing m7G-caps by the enzyme TGS1 and are modifications known for snoRNA, snRNA, and telomerase RNA. New findings originating from HIV-1 research reveal that TMG-caps are present on mRNA and license translation via an mTOR-independent pathway. Research has identified TMG-capping of selenoprotein mRNAs, junD, TGS1, DHX9, and retroviral transcripts. TMG-mediated translation may be a missing piece for understanding protein synthesis in cells with little mTOR activity, including HIV-infected resting T cells and nonproliferating cancer cells. Viruses display a nuanced interface with mTOR and have developed strategies that take advantage of the delicate interplay between these translation pathways. This review covers the current knowledge of the TMG-translation pathway. We discuss the intimate relationship between metabolism and translation and explore how this is exploited by HIV-1 in the context of CD4+ T cells. We postulate that co-opting both translation pathways provides a winning strategy for HIV-1 to dictate the sequential synthesis of its proteins and balance viral production with host cell survival. |
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| id | doaj-art-f65bdafb3bc14f1eab0eeb7aa2c14c8a |
| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-f65bdafb3bc14f1eab0eeb7aa2c14c8a2025-08-20T03:44:03ZengMDPI AGViruses1999-49152025-03-0117337210.3390/v17030372Emerging Roles of m7G-Cap Hypermethylation and Nuclear Cap-Binding Proteins in Bypassing Suppression of eIF4E-Dependent TranslationKathleen Boris-Lawrie0Jessica Liebau1Abdullgadir Hayir2Xiao Heng3Department of Veterinary and Biomedical Sciences, Institute for Molecular Virology, University of Minnesota, Saint Paul, MN 55108, USADepartment of Veterinary and Biomedical Sciences, Institute for Molecular Virology, University of Minnesota, Saint Paul, MN 55108, USADepartment of Veterinary and Biomedical Sciences, Institute for Molecular Virology, University of Minnesota, Saint Paul, MN 55108, USADepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USATranslation regulation is essential to the survival of hosts. Most translation initiation falls under the control of the mTOR pathway, which regulates protein production from mono-methyl-guanosine (m7G) cap mRNAs. However, mTOR does not regulate all translation; hosts and viruses alike employ alternative pathways, protein factors, and internal ribosome entry sites to bypass mTOR. Trimethylguanosine (TMG)-caps arise from hypermethylation of pre-existing m7G-caps by the enzyme TGS1 and are modifications known for snoRNA, snRNA, and telomerase RNA. New findings originating from HIV-1 research reveal that TMG-caps are present on mRNA and license translation via an mTOR-independent pathway. Research has identified TMG-capping of selenoprotein mRNAs, junD, TGS1, DHX9, and retroviral transcripts. TMG-mediated translation may be a missing piece for understanding protein synthesis in cells with little mTOR activity, including HIV-infected resting T cells and nonproliferating cancer cells. Viruses display a nuanced interface with mTOR and have developed strategies that take advantage of the delicate interplay between these translation pathways. This review covers the current knowledge of the TMG-translation pathway. We discuss the intimate relationship between metabolism and translation and explore how this is exploited by HIV-1 in the context of CD4+ T cells. We postulate that co-opting both translation pathways provides a winning strategy for HIV-1 to dictate the sequential synthesis of its proteins and balance viral production with host cell survival.https://www.mdpi.com/1999-4915/17/3/372cap exchangeCBP80/NCBP3DHX9/RNA helicase A-responsive structureepigenetic modificationm2,2,7-guanosine captrimethylguanosine cap (TMG-cap) |
| spellingShingle | Kathleen Boris-Lawrie Jessica Liebau Abdullgadir Hayir Xiao Heng Emerging Roles of m7G-Cap Hypermethylation and Nuclear Cap-Binding Proteins in Bypassing Suppression of eIF4E-Dependent Translation Viruses cap exchange CBP80/NCBP3 DHX9/RNA helicase A-responsive structure epigenetic modification m2,2,7-guanosine cap trimethylguanosine cap (TMG-cap) |
| title | Emerging Roles of m7G-Cap Hypermethylation and Nuclear Cap-Binding Proteins in Bypassing Suppression of eIF4E-Dependent Translation |
| title_full | Emerging Roles of m7G-Cap Hypermethylation and Nuclear Cap-Binding Proteins in Bypassing Suppression of eIF4E-Dependent Translation |
| title_fullStr | Emerging Roles of m7G-Cap Hypermethylation and Nuclear Cap-Binding Proteins in Bypassing Suppression of eIF4E-Dependent Translation |
| title_full_unstemmed | Emerging Roles of m7G-Cap Hypermethylation and Nuclear Cap-Binding Proteins in Bypassing Suppression of eIF4E-Dependent Translation |
| title_short | Emerging Roles of m7G-Cap Hypermethylation and Nuclear Cap-Binding Proteins in Bypassing Suppression of eIF4E-Dependent Translation |
| title_sort | emerging roles of m7g cap hypermethylation and nuclear cap binding proteins in bypassing suppression of eif4e dependent translation |
| topic | cap exchange CBP80/NCBP3 DHX9/RNA helicase A-responsive structure epigenetic modification m2,2,7-guanosine cap trimethylguanosine cap (TMG-cap) |
| url | https://www.mdpi.com/1999-4915/17/3/372 |
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