The general transcription factor TFIIB is a target for transcriptome control during cellular stress and viral infection DOI Open Access
Leah Gulyas, Britt A. Glaunsinger

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 17, 2024

Abstract Many stressors, including viral infection, induce a widespread suppression of cellular RNA polymerase II (RNAPII) transcription, yet the mechanisms underlying transcriptional repression are not well understood. Here we find that crucial component holoenzyme, general transcription factor IIB (TFIIB), is targeted for post-translational turnover by two pathways, each which contribute to its depletion during stress. Upon DNA damage, translational stress, apoptosis, or replication oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV), TFIIB cleaved activated caspase-3, leading preferential downregulation pro-survival genes. further rapid proteasome-mediated E3 ubiquitin ligase TRIM28. KSHV counteracts TFIIB, thereby preserving sufficient pool Thus, may be lynchpin outcomes stress and key target nuclear replicating viruses rely on host machinery. Graphical Significance Statement Transcription synthesizes all protein-coding mRNA. stressors infections dampen RNAPII activity, though processes this fully describe two-pronged degradation strategy cells respond depleting abundance factor, TFIIB. We demonstrate an human gammaherpesvirus antagonizes process, retaining enough support own robust transcription. modulation machinery plays role in dictating outcome perturbation.

Язык: Английский

TRIM25 predominately associates with anti-viral stress granules DOI Creative Commons
Zehua Shang, Sitao Zhang, Jinrui Wang

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 15, 2024

Abstract Stress granules (SGs) are induced by various environmental stressors, resulting in their compositional and functional heterogeneity. SGs play a crucial role the antiviral process, owing to potent translational repressive effects ability trigger signal transduction; however, it is poorly understood how these differ from other stressors. Here we identify that TRIM25, known driver of ubiquitination-dependent innate immune response, critical marker SGs. TRIM25 undergoes liquid-liquid phase separation (LLPS) co-condenses with SG core protein G3BP1 dsRNA-dependent manner. The co-condensation results significant enhancement TRIM25’s ubiquitination activity towards multiple proteins, which mainly located This activating RIG-I signaling pathway, thus restraining RNA virus infection. Our studies provide conceptual framework for better understanding heterogeneity stress granule components response distinct

Язык: Английский

Процитировано

13
Oligoadenylate synthetase 1 displays dual antiviral mechanisms in driving translational shutdown and protecting interferon production DOI Creative Commons
Munesh Kumar Harioudh,

Joseph Pérez,

Zhenlu Chong

и другие.

Immunity, Год журнала: 2024, Номер 57(3), С. 446 - 461.e7

Опубликована: Фев. 28, 2024

Язык: Английский

Процитировано

10
Effector-triggered processing body formation attenuates host translation via ER stress responses and autophagy upon bacterial infection DOI Creative Commons
Manuel González‐Fuente,

Nico Schulz,

Alibek Abdrakhmanov

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Abstract Pathogens employ sophisticated strategies to modulate host protein homeostasis by targeting proteolytic pathways, but their impact on synthesis remains elusive. We report that pathogenic bacteria Pseudomonas syringae ( Pst ) targets ribonucleoprotein condensates, known as processing bodies (P-bodies), attenuate translation through two effectors with liquid-like properties. uncovered a previously unknown link -mediated repression of the ER stress response is required for P-body assembly. Furthermore, we identify novel intersection between P-bodies and autophagy, demonstrating autophagic clearance crucial maintaining balance translationally active inactive mRNAs. Altogether, our discoveries provide insights how attenuated dampen plant immunity uncover connections responses autophagy dynamics.

Язык: Английский

Процитировано

1
Coronavirus takeover of host cell translation and intracellular antiviral response: a molecular perspective DOI Creative Commons
Evangelos D. Karousis, Katharina Schubert, Nenad Ban

и другие.

The EMBO Journal, Год журнала: 2024, Номер 43(2), С. 151 - 167

Опубликована: Янв. 10, 2024

Coronaviruses are a group of related RNA viruses that cause respiratory diseases in humans and animals. Understanding the mechanisms translation regulation during coronaviral infections is critical for developing antiviral therapies preventing viral spread. Translation single-stranded genome host cell cytoplasm an essential step life cycle coronaviruses, which affects cellular mRNA landscape many ways. Here we discuss various strategies control, including how members Betacoronavirus genus shut down suppress innate immune functions, as well role non-structural protein 1 (Nsp1) process. We also outline fate RNA, considering stress response triggered infected cells, describe unique features contribute to programmed ribosomal -1 frameshifting, editing, shutdown evasion.

Язык: Английский

Процитировано

9
Chronic CRYPTOCHROME deficiency enhances cell-intrinsic antiviral defences DOI Creative Commons
Christine T. Styles, Jack Munns, Aiwei Zeng

и другие.

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2025, Номер 380(1918)

Опубликована: Янв. 23, 2025

The within-host environment changes over circadian time and influences the replication severity of viruses. Genetic knockout transcription factors CRYPTOCHROME 1 2 ( CRY1 −/− / CRY2 ; CKO) leads to altered protein homeostasis chronic activation integrated stress response (ISR). adaptive ISR signalling pathways help restore cellular by downregulating synthesis in endoplasmic reticulum overloading or viral infections. By quantitative mass spectrometry analysis, we reveal that many recognition proteins type I interferon (IFN) effectors are significantly upregulated lung fibroblast cells from CKO mice compared with wild-type (WT) mice. This basal ‘antiviral state’ restricts growth influenza A virus is governed interaction between proteotoxic constitutive IFN signalling. proteome composition signature were partially phenocopied upon sustained depletion (CRY) using a small-molecule CRY degrader, modest differential gene expression consistent differences seen WT cells. Our results highlight crosstalk rhythms, cell-intrinsic antiviral defences homeostasis, providing tractable molecular model investigate interface these key contributors human health disease. article part Theo Murphy meeting issue ‘Circadian rhythms infection immunity’.

Язык: Английский

Процитировано

1
SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA DOI Creative Commons
Ranen Aviner, Peter V. Lidsky, Yinghong Xiao

и другие.

PLoS Pathogens, Год журнала: 2024, Номер 20(2), С. e1011535 - e1011535

Опубликована: Фев. 9, 2024

A better mechanistic understanding of virus-host dependencies can help reveal vulnerabilities and identify opportunities for therapeutic intervention. Of particular interest are essential interactions that enable production viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses reporter assays to detect changes protein synthesis dynamics during SARS-CoV-2 (CoV2) infection. We specific translation factors molecular chaperones used by CoV2 promote maturation its own proteins. These be targeted inhibit infection, without major toxicity host. also find non-structural 1 (Nsp1) cooperates with initiation EIF1 1A selectively enhance RNA. When EIF1/1A depleted, more ribosomes initiate from a conserved upstream CUG start codon found all genomic subgenomic RNAs. This results higher open reading frame (uORF1) lower main ORF, altering stoichiometry proteins attenuating Replacing AUG strongly inhibits ORF independently Nsp1, EIF1, or EIF1A. Taken together, our work describes multiple on host biosynthetic networks proposes model dosage control through Nsp1-mediated site selection.

Язык: Английский

Процитировано

6
Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review DOI Creative Commons
Pinja Kettunen, Jari Koıstınaho, Taisia Rõlova

и другие.

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Июнь 6, 2024

Abstract Central nervous system infections have been suggested as a possible cause for neurodegenerative diseases, particularly sporadic cases. They trigger neuroinflammation which is considered integrally involved in processes. In this review, we will look at data linking variety of viral, bacterial, fungal, and protozoan to Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, multiple sclerosis unspecified dementia. This narrative review aims bring together broad range currently supporting the involvement central development diseases. The idea that no single pathogen or group responsible diseases be discussed. Instead, suggest wide susceptibility factors may make individuals differentially vulnerable different infectious pathogens subsequent pathologies.

Язык: Английский

Процитировано

6
The art of hijacking: how Nsp1 impacts host gene expression during coronaviral infections DOI Creative Commons
Evangelos D. Karousis

Biochemical Society Transactions, Год журнала: 2024, Номер 52(1), С. 481 - 490

Опубликована: Фев. 22, 2024

Non-structural protein 1 (Nsp1) is one of the first proteins produced during coronaviral infections. It plays a pivotal role in hijacking and rendering host gene expression under service virus. With focus on SARS-CoV-2, this review presents how Nsp1 selectively inhibits synthesis induces mRNA degradation but not viral mRNAs blocks nuclear export. The clinical implications are highlighted by showcasing pathogenic through repression interferon pathways features variants with mutations coding sequence. ability SARS-CoV-2 to hinder immune responses at an early step, absence homology any human proteins, availability structural information render ideal drug target therapeutic potential.

Язык: Английский

Процитировано

5
Arabidopsis eIF4E1 protects the translational machinery during TuMV infection and restricts virus accumulation DOI Creative Commons
Delyan Zafirov,

Nathalie Giovinazzo,

Cécile Lecampion

и другие.

PLoS Pathogens, Год журнала: 2023, Номер 19(11), С. e1011417 - e1011417

Опубликована: Ноя. 20, 2023

Successful subversion of translation initiation factors eIF4E determines the infection success potyviruses, largest group viruses affecting plants. In natural variability many plant species, resistance to potyvirus is provided by polymorphisms at that renders them inadequate for virus hijacking but still functional in initiation. crops where such alleles are limited, genetic inactivation has been proposed engineering resistance. However, recent findings indicate knockout may be deleterious health and could jeopardize efficiency comparison proteins. Here, we explored cause these adverse effects studying role Arabidopsis eIF4E1, whose was previously reported as conferring clover yellow vein (ClYVV) while also promoting susceptibility another turnip mosaic (TuMV). We report eIF4E1 required maintain global restrict TuMV accumulation during infection, its absence associated with a favoured multiplication over host translation. Furthermore, our show that, results production truncated eIFiso4G1 protein. Finally, demonstrate supporting fitness infection. These suggest counteracts translational apparatus underscore importance preserving functionality when implementing strategies.

Язык: Английский

Процитировано

11
HIV-1-induced translocation of CPSF6 to biomolecular condensates DOI

Katarzyna Bialas,

Felipe Diaz‐Griffero

Trends in Microbiology, Год журнала: 2024, Номер 32(8), С. 781 - 790

Опубликована: Янв. 23, 2024

Язык: Английский

Процитировано

4