A novel peptide encoded by circSRCAP confers resistance to enzalutamide by inhibiting the ubiquitin-dependent degradation of AR-V7 in castration-resistant prostate cancer

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 23, 2025

The sustained activation of androgen receptor splice variant-7 (AR-V7) is a key factor in the resistance castration-resistant prostate cancer (CRPC) to second-generation anti-androgens such as enzalutamide (ENZ). AR/AR-V7 protein regulated by E3 ubiquitin ligase STUB1 and complex involving HSP70, but precise mechanism remains unclear. High-throughput RNA sequencing was used identify differentially expressed circular RNAs (circRNAs) ENZ-resistant control CRPC cells. coding potential circSRCAP confirmed polysome profiling LC–MS. function validated vitro vivo using gain- loss-of-function assays. Mechanistic insights were obtained through immunoprecipitation analyses. A novel circRNA, circSRCAP, identified shown be upregulated C4-2B (ENZR-C4-2B) cells, correlating with increased AR-V7 levels. generated via splicing eIF4A3, forming loop structure exported from nucleus helicase DDX39A. Mechanistically, encodes 75-amino acid peptide (circSRCAP-75aa) that inhibits ubiquitination AR/AR-V7's co-chaperone HSP70 disrupting interaction STUB1. This process results upregulation expression promotes ENZ Xenograft tumor models further role progression its therapeutic target for CRPC. provides an epigenetic influencing stability offers promising treating

Язык: Английский

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DDX RNA helicases: key players in cellular homeostasis and innate antiviral immunity

Journal of Virology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 30, 2024

RNA helicases are integral in metabolism, performing important roles cellular homeostasis and stress responses. In particular, the DExD/H-box (DDX) helicase family possesses a conserved catalytic core that binds structural features rather than specific sequences targets. DDXs have critical all aspects of metabolism including ribosome biogenesis, translation, export, stability. Importantly, functional specialization within this arises from divergent N C termini is driven at least part by gene duplications with 18 42 human having paralogs. addition to their key homeostatic control RNA, these factors virus infection. The canonical RIG-I-like receptors (RLRs) play pivotal cytoplasmic sensing viral structures, inducing antiviral expression. Additional function as sensors or regulators, further diversifying innate immune defense arsenal. Moreover, some been coopted viruses facilitate replication. Altogether, DDX exhibit specificity, playing intricate host defense. This review will discuss mechanisms which recognize diverse structures RNAs, how impacts processing

Язык: Английский

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Critical Cellular Functions and Mechanisms of Action of the RNA Helicase UAP56

Journal of Molecular Biology, Год журнала: 2024, Номер 436(12), С. 168604 - 168604

Опубликована: Май 8, 2024

Язык: Английский

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Exploring the expanding universe of host-virus interactions mediated by viral RNA

Molecular Cell, Год журнала: 2024, Номер 84(19), С. 3706 - 3721

Опубликована: Окт. 1, 2024

Язык: Английский

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NUCLEAR RNA-BINDING PROTEINS MEET CYTOPLASMIC VIRUSES

RNA, Год журнала: 2025, Номер unknown, С. rna.080313.124 - rna.080313.124

Опубликована: Янв. 13, 2025

Cytoplasmic viruses interact intricately with the nuclear pore complex and import/export machineries, affecting nuclear-cytoplasmic trafficking. This can lead to selective accumulation of RNA-binding proteins (RBPs) in cytoplasm. Pioneering research has shown that relocated RBPs serve as an intrinsic defence mechanism against viruses, which involves RNA export, splicing nucleolar factors. For instance, U2 small ribonucleoprotein (snRNP) relocates cytoplasm infected cells uses snRNA viral genomes, repressing replication gene expression. Here, we describe these emerging host-virus interactions discuss remaining questions elucidate their antiviral mechanisms.

Язык: Английский

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DExD-box RNA helicases in human viral infections: pro- and anti-viral functions

Antiviral Research, Год журнала: 2025, Номер unknown, С. 106098 - 106098

Опубликована: Янв. 1, 2025

Язык: Английский

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The potential of RNA-binding proteins as host-targeting antivirals against RNA viruses

International Journal of Antimicrobial Agents, Год журнала: 2025, Номер unknown, С. 107522 - 107522

Опубликована: Апрель 1, 2025

Язык: Английский

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Genome-wide systematic survey and analysis of the RNA helicase gene family and their response to abiotic stress in sweetpotato

BMC Plant Biology, Год журнала: 2024, Номер 24(1)

Опубликована: Март 16, 2024

Abstract Sweetpotato ( Ipomoea batatas (L.) Lam.) holds a crucial position as one of the staple foods globally, however, its yields are frequently impacted by environmental stresses. In realm plant evolution and response to abiotic stress, RNA helicase family assumes significant role. Despite this importance, comprehensive understanding gene in sweetpotato has been lacking. Therefore, we conducted genome-wide analysis family, encompassing aspects such chromosome distribution, promoter elements, motif compositions. This study aims shed light on intricate mechanisms underlying stress responses evolutionary adaptations sweetpotato, thereby facilitating development strategies for enhancing resilience productivity. 300 genes were identified categorized into three subfamilies, namely IbDEAD, IbDEAH IbDExDH. The collinearity relationship between 8 related homologous from other species was explored, providing reliable foundation further family's evolution. Furthermore, through RNA-Seq qRT-PCR verification, it observed that expression eight exhibited responsiveness four stresses (cold, drought, heat, salt) across various tissues ten different varieties. transgenic lines overexpressing IbDExDH96 generated using A.rhizogenes -mediated technology. approach allowed preliminary investigation role cold stress. Notably, promoters contained numerous cis-acting elements associated with temperature, hormone, response, highlighting their response.

Язык: Английский

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TRIM32 inhibits Venezuelan Equine Encephalitis Virus Infection by targeting a late step in viral entry

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

Опубликована: Июнь 4, 2024

Alphaviruses are mosquito borne RNA viruses that a reemerging public health threat. have broad host range, and can cause diverse disease outcomes like arthritis, encephalitis. The ubiquitin proteasome system (UPS) plays critical roles in regulating cellular processes to control the infections with various viruses, including alphaviruses. Previous studies suggest alphaviruses hijack UPS for virus infection, but molecular mechanisms remain poorly characterized. In addition, whether certain E3 ligases or deubiquitinases act as alphavirus restriction factors remains understood. Here, we employed cDNA expression screen identify ligase TRIM32 novel intrinsic factor against VEEV-TC83, SINV, ONNV. Ectopic of reduces whereas depletion CRISPR-Cas9 increases infection. We demonstrate inhibits through mechanism is independent TRIM32-STING-IFN axis. Combining reverse genetics biochemical assays, found interferes genome translation after membrane fusion, prior replication incoming viral genome. Furthermore, our data indicate monoubiquitination important its antiviral activity. Notably, also show two pathogenic mutants R394H D487N, related Limb-girdle muscular dystrophy (LGMD), loss activity VEEV-TC83. Collectively, these results reveal acts suppressing infection provides insights into interaction between UPS.

Язык: Английский

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TRIM32 inhibits Venezuelan equine encephalitis virus infection by targeting a late step in viral entry

PLoS Pathogens, Год журнала: 2024, Номер 20(11), С. e1012312 - e1012312

Опубликована: Ноя. 11, 2024

Alphaviruses are mosquito borne RNA viruses that a reemerging public health threat. have broad host range, and can cause diverse disease outcomes like arthritis, encephalitis. The ubiquitin proteasome system (UPS) plays critical roles in regulating cellular processes to control the infections with various viruses, including alphaviruses. Previous studies suggest alphaviruses hijack UPS for virus infection, but molecular mechanisms remain poorly characterized. In addition, whether certain E3 ligases or deubiquitinases act as alphavirus restriction factors remains understood. Here, we employed cDNA expression screen identify ligase TRIM32 novel intrinsic factor against VEEV-TC83, SINV, ONNV. Ectopic of reduces whereas depletion CRISPR-Cas9 increases infection. We demonstrate inhibits through mechanism is independent TRIM32-STING-IFN axis. Combining reverse genetics biochemical assays, found interferes genome translation after membrane fusion, prior replication incoming viral genome. Furthermore, our data indicate monoubiquitination important its antiviral activity. Notably, also show two pathogenic mutants R394H D487N, related Limb-girdle muscular dystrophy (LGMD), loss activity VEEV-TC83. Collectively, these results reveal acts suppressing infection provides insights into interaction between UPS.

Язык: Английский

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