HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition

Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids. Furthermore, using a single-molecule approach, we show that the sequential interaction of Tax with a RNA-bound UPF1 freezes UPF1: this latter is less sensitive to the presence of ATP and shows translocation defects, highlighting the importance of this feature for NMD. These mechanistic insights reveal how HTLV-1 hijacks the central component of NMD to ensure expression of its own genome. UPF1 is a central protein in nonsense-mediated mRNA decay (NMD), but contribution of its RNA processivity to NMD is unclear. Here, the authors show how the retroviral Tax protein interacts with and inhibits UPF1, and demonstrate that UPF1’s translocase activity contributes to NMD.

• Publication year

  2018

• Venue

  Nature Communications

• Publication date

  2018-01-30

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41467-017-02793-6PMID 29382845PMCID 5789848
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Virus Escape and Manipulation of Cellular Nonsense-Mediated mRNA Decay

  2017cited by this paper
• Faculty Opinions recommendation of Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities.

  2017cited by this paper
• ATP hydrolysis by UPF1 is required for efficient translation termination at premature stop codons

  2016cited by this paper
• Nonsense‐mediated mRNA decay: novel mechanistic insights and biological impact

  2016cited by this paper
• Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway

  2016cited by this paper
• The rules and impact of nonsense-mediated mRNA decay in human cancers

  2016cited by this paper
• Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus

  2016cited by this paper
• Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense-mediated mRNA decay

  2016cited by this paper
• Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability

  2016cited by this paper
• HIV-1 Recruits UPF1 but Excludes UPF2 to Promote Nucleocytoplasmic Export of the Genomic RNA

  2015cited by this paper
• How Retroviruses Escape the Nonsense-Mediated mRNA Decay

  2015cited by this paper
• Target Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity.

  2015cited by this paper
• Identification of elements in human long 3′ UTRs that inhibit nonsense-mediated decay

  2015cited by this paper
• Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities

  2015cited by this paper
• Structures of SMG1-UPFs complexes: SMG1 contributes to regulate UPF2-dependent activation of UPF1 in NMD.

  2014cited by this paper
• A post-translational regulatory switch on UPF1 controls targeted mRNA degradation

  2014cited by this paper
• In Vivo Determination of Direct Targets of the Nonsense-Mediated Decay Pathway in Drosophila

  2014cited by this paper
• Phospho-dependent and phospho-independent interactions of the helicase UPF1 with the NMD factors SMG5–SMG7 and SMG6

  2014cited by this paper
• Nonsense-Mediated Decay Serves as a General Viral Restriction Mechanism in Plants

  2014cited by this paper
• The host nonsense-mediated mRNA decay pathway restricts Mammalian RNA virus replication.

  2014cited by this paper
• Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3′ UTRs

  2013cited by this paper
• Global analyses of UPF1 binding and function reveal expanded scope of nonsense-mediated mRNA decay

  2013cited by this paper
• Viral interference with host mRNA surveillance, the nonsense-mediated mRNA decay (NMD) pathway, through a new function of HTLV-1 Rex: implications for retroviral replication.

  2013cited by this paper
• UPF1 Is Crucial for the Infectivity of Human Immunodeficiency Virus Type 1 Progeny Virions

  2013cited by this paper
• Tight intramolecular regulation of the human Upf1 helicase by its N- and C-terminal domains

  2012cited by this paper
• The Human T-Lymphotropic Virus Type 1 Tax Protein Inhibits Nonsense-Mediated mRNA Decay by Interacting with INT6/EIF3E and UPF1

  2012cited by this paper
• N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and SMG-5:SMG-7 during NMD

  2011cited by this paper
• Molecular mechanisms for the RNA-dependent ATPase activity of Upf1 and its regulation by Upf2.

  2011cited by this paper
• Human UPF1 interacts with TPP1 and telomerase and sustains telomere leading‐strand replication

  2011cited by this paper
• Insights into the recruitment of the NMD machinery from the crystal structure of a core EJC-UPF3b complex.

  2010cited by this paper
• Structural features in the Rous sarcoma virus RNA stability element are necessary for sensing the correct termination codon

  2010cited by this paper
• Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay.

  2010cited by this paper
• Coupling DNA unwinding activity with primer synthesis in the bacteriophage T4 primosome

  2009cited by this paper
• Genome-Wide Identification of Alternative Splice Forms Down-Regulated by Nonsense-Mediated mRNA Decay in Drosophila

  2009cited by this paper
• Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex.

  2009cited by this paper
• Unusual bipartite mode of interaction between the nonsense‐mediated decay factors, UPF1 and UPF2

  2009cited by this paper
• A Competition between Stimulators and Antagonists of Upf Complex Recruitment Governs Human Nonsense-Mediated mRNA Decay

  2008cited by this paper
• Structural Characterization of the Rous Sarcoma Virus RNA Stability Element

  2008cited by this paper
• Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay.

  2008cited by this paper
• NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity

  2008cited by this paper
• Unexpected roles for UPF1 in HIV-1 RNA metabolism and translation.

  2008cited by this paper
• Posttranscriptional Gene Regulation by Spatial Rearrangement of the 3′ Untranslated Region

  2008cited by this paper
• Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways

  2008cited by this paper
• Structural and functional insights into the human Upf1 helicase core

  2007cited by this paper
• Human INT6/eIF3e is required for nonsense‐mediated mRNA decay

  2007cited by this paper
• A 3' UTR sequence stabilizes termination codons in the unspliced RNA of Rous sarcoma virus.

  2006cited by this paper
• The human RNA surveillance factor UPF1 is required for S phase progression and genome stability.

  2006cited by this paper
• Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay.

  2006cited by this paper
• The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity

  2005cited by this paper
• Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay.

  2005cited by this paper
• Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1

  2005cited by this paper
• Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise

  2004cited by this paper
• Efficient downregulation of immunoglobulin mu mRNA with premature translation-termination codons requires the 5'-half of the VDJ exon.

  2004cited by this paper
• Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7.

  2003cited by this paper
• Reversible cross-linking combined with immunoprecipitation to study RNA-protein interactions in vivo.

  2002cited by this paper
• Examining Human T-Lymphotropic Virus Type 1 Infection and Replication by Cell-Free Infection with Recombinant Virus Vectors

  2001cited by this paper
• Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay.

  2001cited by this paper
• Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay.

  2000cited by this paper
• A generic protein purification method for protein complex characterization and proteome exploration

  1999cited by this paper
• The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs.

  1998cited by this paper
• A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsense-containing mRNAs in mammalian cells.

  1998cited by this paper
• Functional and biochemical interaction of the HTLV‐I Tax1 transactivator with TBP.

  1993cited by this paper
• Reexamination of the coding potential of the HTLV-1 pX region.

  1992cited by this paper
• HTLV-I Tax is a zinc-binding protein: role of zinc in Tax structure and function.

  1992cited by this paper
• Gene products that promote mRNA turnover in Saccharomyces cerevisiae

  1992cited by this paper
• Regulation of Rous sarcoma virus RNA splicing and stability

  1988cited by this paper
• Rous sarcoma virus.

  1986cited by this paper
• Identi fi cation and Characterization of Small Molecules That Inhibit Nonsense-Mediated RNA Decay and Suppress Nonsense p53 Mutations

  year unknowncited by this paper

• Effects of the cross-talk between PARP12/PARP13 and nonsense mediated RNA decay pathway on RNA stability and replication of SARS-CoV-2

  2025cites this paper
• Retroviral adapters hijack the RNA helicase UPF1 in a CRM1/XPO1-dependent manner and reveal proviral roles of UPF1

  2025influential citation
• [The invader's defense: how SARS-CoV-2 bypasses and hijacks a frontline cellular defense].

  2025cites this paper
• The dynamic interactions between virus infections and nonsense-mediated decay

  2025cites this paper
• UPF1 shuttles between nucleus and cytoplasm independently of its RNA-binding and ATPase activities

  2025cites this paper
• Hijacking a real time detection thermocycler for enzymology: improvement of a fluorescent bulk assay monitoring helicase activity.

  2025cites this paper
• The SARS-CoV-2 nucleocapsid protein interferes with the full enzymatic activation of UPF1 and its interaction with UPF2

  2025cites this paper
• The SARS-CoV-2 nucleocapsid protein inhibits the cellular Nonsense-Mediated mRNA Decay (NMD) pathway preventing the full enzymatic activation of UPF1

  2024cites this paper
• “It’s Only a Model”: When Protein Structure Predictions Need Experimental Validation, the Case of the HTLV-1 Tax Protein

  2024cites this paper
• Nonsense-mediated mRNA decay pathway in plants under stress: general gene regulatory mechanism and advances

  2024cites this paper
• Molecular Interaction of Nonsense-Mediated mRNA Decay with Viruses

  2023influential citation
• The Upf1 protein restricts EV-A71 viral replication.

  2023cites this paper
• Nonsense-Mediated mRNA Decay Factor Functions in Human Health and Disease

  2023cites this paper
• Replication of the coronavirus genome: A paradox among positive-strand RNA viruses

  2022cites this paper
• Elucidation of the Mechanism of Host NMD Suppression by HTLV-1 Rex: Dissection of Rex to Identify the NMD Inhibitory Domain

  2022cites this paper
• [Tax, the puppet master of HTLV-1 transcription].

  2022cites this paper
• No-nonsense: insights into the functional interplay of nonsense-mediated mRNA decay factors

  2022cites this paper
• The broader sense of nonsense.

  2022cites this paper
• UPF1 mutants with intact ATPase but deficient helicase activities promote efficient nonsense-mediated mRNA decay

  2022cites this paper
• Nonsense-mediated decay controls the reactivation of the oncogenic herpesviruses EBV and KSHV

  2021cites this paper
• Rotaviral nonstructural protein 5 (NSP5) promotes proteasomal degradation of up-frameshift protein 1 (UPF1), a principal mediator of nonsense-mediated mRNA decay (NMD) pathway, to facilitate infection.

  2021cites this paper
• Mechanisms and Regulation of Nonsense-Mediated mRNA Decay and Nonsense-Associated Altered Splicing in Lymphocytes

  2020cites this paper
• Targeting of viral RNAs by Upf1-mediated RNA decay pathways.

  2020cites this paper
• GAS5 protects against osteoporosis by targeting UPF1/SMAD7 axis in osteoblast differentiation

  2020cites this paper
• Viral subversion of nonsense-mediated mRNA decay

  2020cites this paper
• An ‘Arms Race’ between the Nonsense-mediated mRNA Decay Pathway and Viral Infections

  2020cites this paper
• An Antiviral Process Targeting HTLV-1: The Complex Relationship between HTLV-1 and Nonsense-mediated mRNA Decay

  2020cites this paper
• The Complex Relationship between HTLV-1 and Nonsense-Mediated mRNA Decay (NMD)

  2020cites this paper
• The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

  2020cites this paper
• SRSF7 maintains its homeostasis through the expression of Split-ORFs and nuclear body assembly

  2020cites this paper
• Strategies for Success. Viral Infections and Membraneless Organelles

  2019cites this paper
• Host mRNA decay proteins influence HIV-1 replication and viral gene expression in primary monocyte-derived macrophages

  2019cites this paper
• Nonsense‐mediated mRNA decay: The challenge of telling right from wrong in a complex transcriptome

  2019cites this paper
• UPF1-like helicase grip on nucleic acids dictates processivity

  2018cites this paper
• Étude biochimique et biophysique de l’ARN hélicase UPF1 : un moteur moléculaire hautement régulé

  2018cites this paper